Method for insertion of a medical device within a body during a medical imaging process

ABSTRACT

A method for tracking movement of a movable portion of an interventional device disposed within a natural or artificial body opening is provided. In particular, image data of fiducials is acquired and therefrom an initial position of an interventional device movable portion with respect to a given coordinate system is determined. Next, real time position data from the encoders is acquired as the movable portion is moved from the initial position, and a displaced position from the initial position is determined. From this acquired information, a position of the movable portion in the coordinate system is determined using both the initial position as determined from the image data and the real time displaced position as determined from the encoders.

The present application is a divisional of U.S. Pat. No. 8,521,257,filed on Nov. 16, 2009, which is a 371 National Stage application ofPCT/US2007/006531 filed Mar. 14, 2007, which claims the benefit of U.S.Provisional Application No. 60/782,705 filed Mar. 14, 2006. Each of theaforementioned patent applications are hereby incorporated by referencein their entirety.

STATEMENT REGARDING FEDERALLY-SPONSORED RESEARCH

The U.S. Government has provided funding under contract No./grant No.EEC9731478 awarded by the National Science Foundation and under contractNo./grant 1R01EB02963 by the National Institute of Health, thus thegovernment may have certain rights to and/or in the invention.

FIELD OF INVENTION

The present invention generally relates to devices, apparatuses andmethods for inserting a medical device such as a needle into a mammalianbody while the body is within the imaging field of a medical imager,particularly devices, apparatuses and methods for inserting and guidinga needle to a target site within a body while the body is within theimaging field of a medical imager, and more particularly to devices,apparatuses and methods for inserting and guiding a needle to a targetsite within a body selected by the user while the body is within theimaging field of a medical imager.

BACKGROUND OF THE INVENTION

Prostate diseases represent a significant health problem in the UnitedStates. After cardiac diseases and lung cancer, metastatic prostatecancer is the third leading cause of death among the American men overfifty years, resulting in approximately 31,000 deaths annually. Thedefinitive diagnostic method of prostate cancer is core needle biopsy.Annually in the U.S., approximately 1 million prostate biopsies areperformed. The average number of new prostate cancer patients detectedby needle biopsy has stabilized around 200,000 per year. Due to theevolution in screening techniques, more cases are diagnosed at anearlier stage, when patients are candidates for some form of minimallyinvasive localized therapy typically delivered with needles. Themajority of the cancer-free biopsied patients are likely to have benignprostate hyperplasia (BPH). Currently more than 10 million American mensuffer from BPH. Significant attention has been focused on minimallyinvasive local therapies of this condition, because its definitivetreatment, transurethral resection (TURP) is a highly invasive surgicalprocedure with potentially adverse side effects. Needle-based ablativetherapies have shown promising results lately in the treatment of BPH.

Currently, transrectal ultrasound (TRUS) guided needle biopsy is primarytechnique being utilized for the diagnosis of prostate cancer [Presti JC Jr. Prostate cancer: assessment of risk using digital rectalexamination, tumor grade, prostate-specific antigen, and systematicbiopsy. Radiol Clin North Am. 2000 January; 38(1):49-58. Review] andcontemporary intraprostatic delivery of therapeutics is also primarilyperformed under TRUS guidance. This technique has been overwhelminglypopular due to its excellent specificity, real-time nature, low cost,and apparent simplicity. At the same time, however, TRUS-guided biopsyfails to correctly detect the presence of prostate cancer inapproximately 20% of cases [Norberg M, Egevad L, Holmberg L, Sparen P,Norlen B J, Busch C. The conventional sextant protocol forultrasound-guided core biopsies of the prostate underestimates thepresence of cancer. Urology. 1997 October; 50(4):562-6; Wefer A E,Hricak H, Vigneron D B, Coakley F V, Lu Y, Wefer J, Mueller-Lisse U,Carroll P R, Kurhanewicz J. Sextant localization of prostate cancer:comparison of sextant biopsy, magnetic resonance imaging and magneticresonance spectroscopic imaging with step section histology. J Urol.2000 August; 164(2):400-4].

For the same reason, targeted local therapy today also is not possiblewith the use of TRUS guidance. Instead, major anatomical regions (ormost often the entire prostate gland) are treated uniformly while tryingto maintain the fragile balance between minimizing toxic side effects insurrounding normal tissues and providing/giving a sufficient therapeuticdose to the actual cancer. Also importantly, the transrectal ultrasoundprobe applies variable normal force on the prostate through the rectalwall, causing dynamically changing deformation and dislocation of theprostate and surrounding tissue during imaging and needle insertion, anissue that has to be eliminated in order to achieve accurate andpredictable needle placement. The key to successful prostate biopsy andlocal therapy is accurate, consistent and predictable needle placementinto the prostate, and some form of image guidance.

MRI imaging has a high sensitivity for detecting prostate tumors.Unfortunately, MR imaging alone, without concurrent biopsy, suffers fromlow diagnostic specificity. In addition, there are other fundamentalobstacles that must be addressed when using MRI imaging techniques inprostate biopsy and related localized therapy of the prostate.Conventional high-field MRI scanners use whole-body magnets thatsurround the patient completely and do not allow access to the patientsduring imaging. Thus, the workspace inside the bore of the whole-bodymagnet is so extremely limited, that conventional medical robots andmechanical linkages do not fit inside the whole-body magnet. Also, thestrength of the magnetic field being generated within the whole-bodymagnet is about 200,000 times stronger than the magnetic field of theearth. Due to these ultra-strong magnetic fields, ferromagneticmaterials and electronic devices are not allowed to be in the magnet dueto safety and/or imaging concerns, which excludes the use of traditionalelectro-mechanical robots and mechanical linkages.

Tempany, D'Amico, et al. [Cormack R A, D'Amico A V, Hata N, Silverman S,Weinstein M, Tempany C M. Feasibility of transperineal prostate biopsyunder interventional magnetic resonance guidance. Urology. 2000 Oct. 1;56(4):663-4; D'Amico A V, Tempany C M, Cormack R, Hata N, Jinzaki M,Tuncali K, Weinstein M, Richie J P. Transperineal magnetic resonanceimage guided prostate biopsy. J Urol. 2000 August; 164(2):385-7']proposed to use an open MRI configuration in order to overcome spatiallimitations of the scanner. The magnet configuration for this open MRIconfiguration allows the physician to step inside the magnet and deliverbiopsy and therapeutic needles into the prostate. This approach showedthat it was possible to use an MRI imaging process to detect cancerpreviously missed by ultrasound guided needle biopsy and to performtargeted brachytherapy of the prostate. This technique has limitations,however, because it involves the use of an open MRI scanner. Perhapsmost importantly, the incurred cost and complexity of open MRI imagingare substantial, especially when compared to transrectal ultrasoundimaging.

Open magnets also tend to have weaker magnetic fields than the magneticfields that are generated using closed magnets, thus open magnets tendto have lower signal-to-noise ratio (SNR) than the SNR for a closedhigh-field MRI scanners. Consequently, intra-operative images for anopen magnet tend to be of a lower quality than the diagnostic imagesfrom a closed MRI scanner. While this approach seems to be acceptablewhen used in a research type of environment, it adds to the complexityand cost of the open MRI. Tempany et al. apply transperineal needleplacement for both biopsy and brachytherapy, which is conventionallyaccepted for therapy, but for biopsy, it is a significantly moreinvasive route than through the rectum.

Traditionally, needles are placed into the prostate manually whileobserving some intra-operative guiding images, typically real-timetransrectal ultrasound. TRUS biopsy is executed with entirely free hand.Transperineal needle placement is significantly more controlled bystepping transrectal ultrasound and template jigs, however, it stilldepends on the physician's hand-eye coordination. Therefore, theoutcomes of TRUS guided procedures show significant variability amongpractitioners.

Recently, a 6-DOF robot has been presented for transperineal needleplacement into the prostate, but that kinematic concept is notapplicable in transrectal procedures [G. Fichtinger, T. L DeWeese, A.Patriciu, A. Tanacs, D. Mazilu, J. H. Anderson, K. Masamune, R H.Taylor, D. Stoianovici: Robotically Assisted Prostate Biopsy And TherapyWith Intra-Operative CT Guidance: Journal of Academic Radiology, Vol 9,No 1, pp. 60-74]. An industrial robot also has been applied to assistTRUS-guided prostate biopsy with the use of a conventional end-shootingprobe [Rovetta A, Sala R: Execution of robot-assisted biopsies withinthe clinical context, Journal of Image Guided Surgery. 1995;1(5):280-287]. In this application, the robot mimicked the manualhandling of TRUS biopsy device in the patient's rectum, in a telesurgeryscenario.

A robotic manipulator has been reported for use inside an open MRIconfiguration, which device is intended to augment the Tempany et al.developed system [Chinzei K, Hata N, Jolesz F A, Kikinis R, M RCompatible Surgical Robot: System Integration and Preliminaryfeasibility study, Medical Image Computing and Computer-assistedIntervention 2000, Pittsburgh, Pa. Lecture Notes in Computer Science,MICCAI 2000, Springer-Verlag, Vol. 1935, pp. 921-930]. The motors ofthis robot are situated outside the first magnetic zone, while themotors actuate two long arms to manipulate the surgical instrument inthe field of imaging. This solution is not suitable for a closed magnetconfiguration. In addition, the long arms of this robotic manipulatoramplify the effects of flexure and sagging, which can render this systeminaccurate for certain procedures. Moreover, because the device isintended to be mounted permanently with respect to the MRI scanner, therobotic manipulator is not flexibly adaptable to different sides of thebody.

Recently, a robot has been developed for use inside a conventional MRIscanner that is custom-designed for breast biopsy, [Kaiser W A, Fischer14, Vaguer J, Selig M. Robotic system for biopsy and therapy of breastlesions in a high-field whole-body magnetic resonance tomography unit.Invest Radiol. 2000 August; 35(8):513-9]. This robot is mounted on thetable of the scanner and it realized six degrees of freedom (6 DOF).This robot is demonstrated in accessing the breast, but it is notreadily adaptable for abdominal and intracavity use. There also has beenpublished variations of an in-MRI robot for stereotactic brain surgery,but the actual embodiments of that system also are not applicable intransrectal biopsy [Masamune et. al., Development of an MRI-compatibleneedle insertion manipulator for stereotactic neurosurgery. Journal ofImage Guided Surgery, 1995, 1 (4), pp. 242-248].

The development of magnetic resonance imaging (MRI) guided roboticintervention instruments also necessarily involves and is complicated bythe need to track in real-time the position and orientation of theseinstruments within the MRI scanner. Consequently a variety of methodshave been developed for the spatial registration and tracking of roboticand manual instruments within MRI scanners. The reported approachesinclude joint encoding, passive fiducial features, optical positionsensing, gradient field sensing and micro-tracking sensing coils.

As is known to those skilled in the art, in the joint encoding approachthe position of the intervention device (e.g., needle or other surgicaldevice) is determined by joint encoders. This approach has itslimitations in that it requires or involves the addition of a rigidmechanical mounting system to the MRI scanner so the intervention deviceis mounted rigidly on the MRI scanner, in a highly repeatable manner andalso requires a precise pre-calibration of the device with respect tothe scanner coordinate system before using the interventional device.

A number of systems or methods have been developed around the use ofpassive MRI fiducials that are attached or registered to theintervention device in a pre-set geometric arrangement. As is known tothose in the art, the fiducials include materials that are visible ordetectable during the MRI process. In one reported system, templateholes of a passive needle guiding template for transperineal MRI-guidedHDR prostate brachytherapy were filled with a contrast material, whichwere pre-operatively localized in standard T1 or T2-weighted images andregistered to the coordinate frame of the MRI scanner. In a reported MRIguided transrectal needle biopsy system a passive fiducial marker sleevecoaxial with the biopsy needle was employed. In this system, the needleposition is manually adjusted while the passive marker is imaged withoblique T2-weighted turbo spin echo (TSE) image sequences. While thisapproach is based on the use of inexpensive and robust passivefiducials, the approach does require or involve repeated volume imagingof high resolution that takes considerable time to acquire.

The optical position sensing approach involves an optical trackingsystem that is deployed and calibrated with respect to the scannercoordinate system. Such a system also requires line-of-sight between theoptical tracking cameras and the device, and requires tetheredlight-emitting diodes (LEDs) to be attached to the instrument. Althoughthis approach provides real-time tracking performance suitable forvisual serving, the line-of-sight requirement of such a system rendersthis approach from unusable with conventional closed-bore MRI scanners.

In the gradient field sensing approach, the gradient field andconventional pulse sequences are used for localization. In regards tothis approach, Hushek et al. investigated an FDA-approved commercialtracking mechanism called EndoScout (Robin Medical Systems, Baltimore,Md.) in the open MRI scanner (the device utilizes conventional imagepulse sequences and gradient field for localization). In presentimplementations, however, the tracking sensors must be placed close tothe MRI magnet's isocenter, and thus may occupy critical volume in theinterventional device. This approach also requires a precise one timecalibration procedure to be performed over the entire field of interestin each MRI system on which it is installed.

Another of the previously reported tracking methods employs a number ofmicro-tracking coils (e.g., three or more micro-tracking coils) that arerigidly attached to an MRI-compatible instrument. In this approach, aseries of custom-programmed MRI pulse sequences provide one dimensionalprojections of the coil positions for each coil. Each individualprojection pulse sequence takes several milliseconds, and the Cartesianposition of all three micro-tacking coils can be completed within 50 ms.The individual micro-coil position data are employed to compute the sixdegree-of-freedom (6-DOF) position and orientation of the instrumentwith respect to the scanner coordinate system. Update rates of 20 Hz forfull 6-DOF tracking have been reported. While the micro-coil trackingapproach advantageously yields high accuracy (e.g., mean positionalerrors of 0.2 mm and 0.3 degrees), high speed (full 6-DOF trackingupdate rates of 20 Hz have been reported) and direct real-time 6-DOFtracking of the tool end-point, there are some shortcomings.

The use of micro-coils for tracking involves the development of customtracking pulse sequences which necessarily must be implemented, andtested for each scanner. These pulse sequences differ from the standardimaging pulse sequences normally available on MRI scanners. Also, fewscanners presently support micro-coil tracking as a standard capability.In addition a custom interface between the scanner software and atracking program must be established to access the tracking coillocations.

Also, the tracking coils require a minimum of three scanner receiverchannels. Most present-day MRI scanners posses four or more receiverchannels, thus this method can be used on most scanners, however thisdoes limits the number of imaging coils that can be used simultaneouslyfor an interventional procedure. Further, this approach requires aminimum of three micro-coils to be incorporated within the navigatedinstrument. This can complicate the design and manufacturing of theinstrument. Moreover, the micro-coils normally require a custom-builttuning, detuning and impedance matching circuit to be developed for eachscanner. Based on experience the frequent failures in the micro-coilsand electrical circuit significantly degrades the reliability of theoverall MRI guided instrument.

It thus would be desirable to provide a new device, apparatus, systemsand methods for image-guided biopsy and/or a wide range of therapeutictechniques including needle therapy that employs high resolution MRIimaging inside a closed MRI scanner. It also would be particularlydesirable to provide such devices, apparatuses, systems and methods forimage guided biopsy and/or therapeutic techniques of the prostate,rectum, vagina or cervix, as well as an artificial opening created inthe body such as for example those used in connection with laparoscopicprocedures/techniques. It would be particularly desirable to providesuch a device, apparatus, system and method that would replace theconventional manual technique with a controlled needle insertion andguiding technique to maximize needle placement accuracy and also tominimize dynamic tissue deformation during the procedure. It also wouldbe particularly desirable to provide such devices, apparatuses, systemsand methods that employ real-time MRI guidance, are compatible withconventional high-field MRI scanners with no artifact, that can fitinside a closed whole-body magnet, that can perform needle insertion(e.g., transrectal needle insertion), that minimizes organ motion anddeformation in a non-invasive manner and which provides threedegree-of-freedom motion to reach a target within the body and selectedby the user/medical personnel. It also would be particularly desirableto provide devices, apparatuses, systems and methods that embody atracking methodology having an accuracy comparable to the accuracy foractive tracking coils, but which does not require the use of such activetracking coils.

SUMMARY OF THE INVENTION

The present invention features devices, systems, apparatuses and methodsfor entering a medical device such as a needle into a mammalian body(e.g., a human body), while the body is inside a medical imager such asa MRI scanner, CT, X-ray fluoroscopy, and ultrasound imaging, fromwithin a body cavity (such as the rectum, vagina, or laparoscopicallyaccessed cavity). A minimum three degree-of-freedom mechanical devicetranslates and rotates devices according to the present invention insidethe cavity and enters the medical device (e.g., a needle) into the body,and steers the needle to a target point selected by the user. The deviceis guided by real-time images from the medical imager. Networkedcomputers process the medical images and enable the clinician to controlthe motion of the mechanical device that is operated directly within theimager, outside of the imager or remotely from outside the imager.

The devices, systems, apparatuses, and methods of the present inventionare particularly adaptable for use in image-guided prostate biopsy thatemploys high resolution MRI imaging inside a closed MRI scanner, whilemaintaining safe transrectal access. In addition, such devices,apparatuses, systems and methods embody a controlled needle insertiontechnique, as compared to the conventional manual manipulationtechnique, thereby maximizing needle placement accuracy and alsominimize dynamic tissue deformation during the procedure. The device,system, apparatus and methods of the present invention also can employreal-time MRI guidance while the system is compatible with high-fieldMRI scanners with no imaging artifacts. In addition, a device and/orapparatus of the present invention fits inside a closed magnet,minimizes organ motion and deformation in a non-invasive manner and usesat least three degree-of-freedom motion to reach a selected target.

According to one aspect of the present invention there is featured aninterventional device for use while a mammalian body is within animaging field of a medical imaging apparatus. Such an interventionaldevice includes an end-effector member a portion of which is insertedinto one of a natural cavity or an artificially formed cavity of amammalian body while the body is within the imaging field of the medicalimaging apparatus. The natural body cavity includes any naturaloccurring orifice of the mammalian body including the rectum and uterus.An artificial formed body cavity includes those cavities formed as aresult of surgical procedures such as laparoscopic surgical procedures.

In one aspect of the invention, the end-effector member includes asheath member having a longitudinally extending interior compartment anda carrier member being one of translatably or rotatably disposed withinthe sheath member interior compartment. According to another aspect ofthe invention, the end-effector member includes a sheath member having alongitudinally extending interior compartment and an inner member beingrotatably and/or translatably disposed within the sheath member interiorcompartment. The sheath member also is configured and arranged so it canbe received with said one of natural or artificial body cavity. Forexample, the sheath member is shaped and sized so as to be received inthe rectum without causing damage to the tissues thereof. Further, theend-effector is configured and arranged to selectively deploy a medicaldevice therefrom between a stored position and a deployed position. Inthe deployed position a portion of the medical device is disposed incertain of tissues (i.e., target tissues) about said one of the naturalor artificial body cavity. The target tissues include the tissue orcells being targeted for one of diagnosis (e.g., biopsy) or treatment.

More particularly, the sheath member and the carrier member and innermember are configured and arranged so rotation and/or translation of thecarrier or inner member is not imparted to the sheath member. In thisway, and in contrast to prior art devices, the movement of the carrieror inner member does not dynamically change deformation or dislocationof the prostate for example. In more specific embodiments, the carrieror inner member can be selectively translated (e.g., movelongitudinally) within the sheath member and then rotated within thesheath member so the end-effector is put into the desired orientationfor performing a biopsy, delivering of a therapeutic medium and/or otheractions as herein described.

In particular embodiments, the sheath member is configured so as toinclude a through aperture that communicates with the sheath memberinterior compartment and which extends partially circumferentially andpartially longitudinally so as to form a window in an exterior surfaceof the sheath member. It also is within the scope of the presentinvention for the medical device to penetrate through or pierce asurface (e.g., end or side surface) of the sheath member as it is beingdeployed from the carrier or inner member to the target tissues. Infurther embodiments, the sheath member also is arranged so it can rotateand the carrier or inner member also can rotate and/or translate withinthe sheath member interior compartment.

In more particular embodiments, the end-effector member further includesan imaging device that is configured and arranged so as to image avolume of tissues including the certain tissues. More particularly, theend-effector member further includes an MRI receive antenna that isconfigured and arranged to image a volume of tissues including thecertain tissues. More specifically, the MRI receive antenna is arrangedso as to image tissues opposite the sheath member through aperture oropposite an area of a surface the sheath member that the medical deviceis to penetrate through.

In more particular embodiments, the end-effector member further includesone or more tracking devices, each of said one or more tracking devicesbeing configured and arranged so a position of each tracking device canbe determined using an imaging system external to the interventionaldevice. In one exemplary embodiment, the one or more tracking devicesare passive fiducials appropriate for the particular imaging techniqueembodied in the external imaging system and the one or more trackingdevices are arranged (e.g., within the carrier member) so as to allow adetermination to be made of an amount the carrier member is beingtranslated or rotated within the sheath member.

In further embodiments, the external imaging system is an MRI imagingsystem and the one or plurality or more tracking devices comprise one ofa passive fiducial or a tracking coil. More particularly, one of thepassive fiducials or the tracking coils are arranged so as to allow adetermination to be made of an amount the carrier member is beingtranslated or rotated within the sheath member. In exemplaryembodiments, the end-effector member includes three tracking coils thatare arranged so as to allow a determination to be made of an amount thecarrier member is being translated or rotated within the sheath member.Such an end-effector member also can include passive fiducialsappropriate for tracking the device in MRI images. Reference also shallbe made to U.S. Pat. Nos. 5,271,400; 6,470,204 and 6,492,814, theteaching of which are incorporated herein by reference as to furtherdetails about tracking coils and the use thereof.

According to yet further aspects/embodiments of the present invention,the interventional device of the present invention provides improvedaccess to a target from within a body cavity through multiple needlechannels and/or with a steerable needle channel and/or embodies easy toimplement scanner independent tracking methods, on-the-fly signalintensity correction, and/or reduction of organ deformation.

In more particular aspects/embodiments, the present invention includenew device mechanics particularly multiple needle channels; steerablechannel; rotating sheath; new device tracking and tracking methods whichcan include tracking by combining passive and position encoder (e.g.,opto-electrical encoder) tracking; signal intensity correction which canbe combined with tracking; and/or new methods and systems for reductionof organ motion with variable geometry prostate stabilization. Theseaspects may be applied singularly or more preferably two or more ofthese aspects can be applied in a device or method in combination.

Also featured are systems, apparatuses and method related thereto. Suchsystems and methods of the present invention can have a variety ofapplications including, but not limited to, prostate biopsy in a closedMRI scanner; prostate local therapy in a closed MRI scanner; and/orpercutaneous medical procedures from within natural body cavity (e.g.,rectum, vagina, uterus, etc) or laparoscopic cavity, underintra-operative image guidance (e.g., MRI, CT, PET, SPECT, PET-CT andcone beam CT).

Systems of the invention can be manually operated or automated, e.g.,devices of the invention can be motorized to obtain fast imagecontrolled tissue biopsies and delivery of needles for therapeuticprocedures without the need of pulling the patient in and out of theimaging scanner. Vacuum assisted biopsy, and motorized exchange ofbiopsy needles can facilitate automated extraction of tissue samples.

Systems of the invention also can impact organ deformation, includingvia software which accounts for organ deformation based on tissue modelsand can adjust targeting parameters prior to inserting a needle in orderto increase targeting accuracy.

Other aspects and embodiments of the invention are discussed below.

DEFINITIONS

The instant invention is most clearly understood with reference to thefollowing definitions:

As used in the specification and claims, the singular form “a”, “an” and“the” include plural references unless the context clearly dictatesotherwise. For example, the term “a cell” includes a plurality of cells,including mixtures thereof. The term “a nucleic acid molecule” includesa plurality of nucleic acid molecules.

As used herein, the term “comprising” or “including” is intended to meanthat the compositions, methods, devices, apparatuses and systems includethe recited elements, but do not exclude other elements. “Consistingessentially of”, when used to define compositions, devices, apparatuses,systems, and methods, shall mean excluding other elements of anyessential significance to the combination. Thus, a compositionconsisting essentially of the elements as defined herein would notexclude trace contaminants from the isolation and purification methodand pharmaceutically acceptable carriers, such as phosphate bufferedsaline, preservatives, and the like. “Consisting of” shall meanexcluding more than trace elements of other ingredients, elements andsubstantial method steps. Embodiments defined by each of thesetransition terms are within the scope of this invention.

As used herein, a “target cell” or “recipient cell” refers to anindividual cell or cell which is desired to be, or has been, a recipientof exogenous nucleic acid molecules, polynucleotides and/or proteins andincludes cells of tissues being targeted by the devices, apparatuses,systems and methods of the present invention. The term is also intendedto include progeny of a single cell, and the progeny may not necessarilybe completely identical (in morphology or in genomic or total DNAcomplement) to the original parent cell due to natural, accidental, ordeliberate mutation. A target cell may be in contact with other cells(e.g., as in a tissue) or may be found circulating within the body of anorganism. As used herein, a “target cell” is generally distinguishedfrom a “host cell” in that a target cell is one which is found in atissue, organ, and/or multicellular organism, while as host cell is onewhich generally grows in suspension or as a layer on a surface of aculture container.

As used herein, a “subject” is a vertebrate, preferably a mammal, morepreferably a human. Mammals include, but are not limited to, murines,simians, humans, farm animals, sport animals, and pets.

The terms “cancer,” “neoplasm,” and “tumor,” are used interchangeablyand in either the singular or plural form, refer to cells that haveundergone a malignant transformation that makes them pathological to thehost organism. Primary cancer cells (that is, cells obtained from nearthe site of malignant transformation) can be readily distinguished fromnon-cancerous cells by well-established techniques, particularlyhistological examination. The definition of a cancer cell, as usedherein, includes not only a primary cancer cell, but any cell derivedfrom a cancer cell ancestor. This includes metastasized cancer cells,and in vitro cultures and cell lines derived from cancer cells. Whenreferring to a type of cancer that normally manifests as a solid tumor,a “clinically detectable” tumor is one that is detectable on the basisof tumor mass; e.g., by procedures such as CAT scan, MR imaging, X-ray,ultrasound or palpation, and/or which is detectable because of theexpression of one or more cancer-specific antigens in a sampleobtainable from a patient.

As used herein, a “composition” refers to the combination of an activeagent (e.g., such as a therapeutic agent, nucleic acid vector) with acontrast agent. The composition additionally can comprise apharmaceutically acceptable carrier or excipient and/or one or moreaccessory molecules which may be suitable for diagnostic or therapeuticuse in vitro or in vivo. The term “pharmaceutically acceptable carrier”as used herein encompasses any of the standard pharmaceutical carriers,such as a phosphate buffered saline solution, water, and emulsions, suchas an oil/water or water/oil emulsion, and various types of wettingagents. The compositions also can include stabilizers and preservatives.For examples of carriers, stabilizers and adjuvants, see MartinRemington's Pharm. Sci., 15th Ed. (Mack Publ. Co., Easton (1975)).

BRIEF DESCRIPTION OF THE DRAWING

For a fuller understanding of the nature and desired objects of thepresent invention, reference is made to the following detaileddescription taken in conjunction with the accompanying drawing figureswherein like reference character denote corresponding parts throughoutthe several views and wherein:

FIG. 1 is an axonometric view of an interventional device according tothe present invention;

FIG. 2 is a perspective view of an interventional device according tothe present invention without an insertion stage for clarity that isaffixed to an illustrative positioning apparatus;

FIG. 3 is a cross-sectional view of the interventional device of FIG. 1;

FIG. 4 is an axonometric view of an end-effector of the apparatus ofFIG. 1;

FIG. 5A is a cross-sectional view of the end-effector of FIG. 4;

FIG. 5B is a cross-sectional view of another end-effector according toan embodiment of the present invention;

FIG. 6 is an illustrative view of the sheath of the end-effector of FIG.4;

FIG. 7 is an illustrative view of the needle guide of the end-effectorof FIG. 4;

FIG. 8 is an axonometric view of a positioning stage of the apparatus ofFIG. 1;

FIG. 9 is a cross-sectional view of the positioning stage of FIG. 8;

FIG. 10A is a perspective view of one embodiment of the insertion stagewith cylindrical cartridges;

FIG. 10B is a perspective view of another embodiment of the insertionstage with quadratic cartridges;

FIG. 11 is a cross-sectional view of the insertion stage of FIG. 10A;

FIG. 12 is a perspective view of an interventional device according toanother aspect of the present invention affixed to another illustrativepositioning apparatus;

FIG. 13 is an illustrative view that illustrates the workings of thepositioning stage of the interventional device of FIG. 12;

FIG. 13A is an illustrative view of a portion of the positioning stageof FIG. 12 that embodies another technique for encoding translationaland/or rotational positional information;

FIG. 14 is a perspective view of an end-effector according to thepresent invention configured to use ultrasound for imaging of the targettissues;

FIG. 15 is a schematic view generally illustrating an interventionalsystem according to the present invention;

FIG. 16 is an illustration of the targeting methodology according to oneaspect of the present invention when using three degrees of freedom;

FIG. 17 is an illustrative view that illustrates placement of theend-effector of the interventional device within the rectum of a canine;

FIG. 18 is a schematic view of an end-effector with the needle in aninserted position for illustrating a calibration method of the presentinvention;

FIG. 19 In an anesthetized canine, four targets were selected from T1weighted FSE images (top row) (TE 9.2 msec, TR 700 msec, BW+/−31.25 KHz,ETL 4, FOV 16 cm, slice thickness 3 mm, 256×256, NEX=4, scan time 3:00).FSE images were repeated after needle placement (bottom row).

FIG. 20 Artifacts created by prostate needle (Panel a) and brachytherapyseed (Panel b) (FSE, TE 9.2 msec, TR 700 msec, BW+/−31.25 KHz, ETL 4,FOV 8 cm, slice thickness 1.5 mm, 256×256, NEX=4, scan time 3:00). Bothobjects create a uniform signal void along their length and a circularbloom, centered on the object tip, at the end facing the positive poleof the main field. Artifacts were aligned by placing the physicalobjects at the interface of gadolinium doped and gadolinium free gelblocks.

FIG. 21 Intraprostatic injections (here, a solution of 0.4% Trypan Blueand 30 mM Gd-DTPA) can be visualized under MRI. The white box on thesagittal scout (left image) shows the location of the time seriesimages. Note that all of the injected contrast/dye solution staysconfined within the prostate. Therefore, it was confirmed that the full,desired dose was delivered to the tissue. (FSPGR, TE 1.5 msec, TR 6msec, FA 90°, BW+/−62.5 KHz, FOV 16 cm, slice thickness 10 mm, 256×160,0.96 sec/image).

FIG. 22 The distribution of injected material visualized in MR imagesreflects the actual, histologically confirmed distribution.Gadolinium-DTPA location (enhancement seen in post- but notpre-injection images) matches with blue stained tissue in the canineprostate (FSPGR, TE 2.0 msec, TR 80 msec, FA 60°, BW+/−31.25 KHz, FOV 16cm, slice thickness 3 mm, 256×256, NEX 4, scan time 1:20).

FIG. 23 MRI monitoring allows for detection of faulty injections. Thewhite box on the sagittal scout (left image) shows the location of thetime series images. In this canine, the injected contrast/dye solutionleaked out of the prostate and into surrounding connective tissue.Therefore, it is known—during the procedure—that the desired dose hasnot been delivered to the prostate.

FIG. 24 In both MR images and histological sections, leakage of theinjected solution into surrounding tissue is confirmed. Gadolinium-DTPAlocation (bright enhancement seen in MR images) correlates with bluestained tissue in canine prostate sections. While some contrast and dyeremained within the prostate, additional solution passed into connectivetissue at the superior, left, posterior prostate margin.

FIG. 25 MRI guidance allows for accurate placement of brachytherapyseeds within the prostate. Three targets were selected in a singlecoronal plane within the prostate (row a) (FSE, TE 9.2 msec, TR 700msec, BW+/−31.25 KHz, ETL 4, FOV 16 cm, slice thickness 3 mm, 256×256,NEX=4, scan time 3:00). The needle was placed at these locations asdescribed previously (row b). As the brachytherapy seeds are placed atthe end of the canula (2 mm back from the end of the trocar tip), theneedle artifact is seen to extend beyond the target site byapproximately 2 mm. In row c, the seeds have been placed within theprostate. The black, bloom artifact at the superior end of the 4 mmbrachytherapy seeds is visible. The seeds extend 4 mm in the inferiordirection from this artifact.

FIG. 26 is a perspective view of an interventional device according toanother aspect of the present invention.

FIG. 27 is a perspective view of another interventional device accordingto another aspect of the present invention.

FIG. 28 is a perspective view of an end-effector according to anotheraspect of the present invention.

FIG. 29A is a perspective view of an interventional device positioningsystem according to another aspect of the present invention.

FIG. 29B is a perspective view of the arm of the interventional devicepositioning system of FIG. 29A.

FIG. 29 C is a schematic view of the arm of FIG. 29B.

FIG. 30 is a perspective schematic view of an interventional deviceillustrating one step in establishing the initial position of theinterventional device.

FIG. 31 is another perspective schematic view illustrating another stepin establishing the initial position of the interventional device.

FIG. 32 is an illustrative view of a test plate. The test plate containschannels for the device axis, the needle axis and a third perpendicularchannel. Markers were placed in each channel. The channels were machinedwith a nominal angle α=40 degrees and distance d=50 mm.

FIG. 33 is an illustrative view of typical axial image slices of apassive fiducial marker employed in the experimental evaluation on a 3-TPhilips Intera MRI scanner. A thin slice of isotropic 1 mm×1 mm×1 mmoblique sagittal PD-weighted TSE images were obtained along the axis ofa tubular gadolinium marker. The sagittal images were reformatted (usingthe scanner's software) to obtain axial images along the axis of themarker to facilitate identification of the marker axial centers.

FIG. 34 is a tabulation of accuracy test results. the left half of thetable presents the results with all circles for each marker used tocalculate an axis. The right half contains accuracy entries where onlyone circle per marker was used to calculate an axis. The results arepresented in columns based upon which markers were used to compute theneedle axis.

FIG. 35 is a graphical view of max and std deviation of error versuslength between needle markers.

FIG. 36A is a graphical view of a prior art histograms of angular errorsfor an active tracking method from A. Krieger, R. C. Susil, C. Menard,J. A. Coleman, G. Fichtinger, E. Atalar, and L. L. Whitcomb. Design of anovel MRI compatible manipulator for image guided prostateinterventions. IEEE Transactions on Biomedical Engineering,52(2):306-313, February 2005.

FIG. 36A is a graphical view of a histogram of angular errors for thehybrid tracking method of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring now to the various figures of the drawings wherein likereference characters refer to like parts, there is shown in FIGS. 1-3various views of a interventional device 100 according to one aspect ofthe present invention. In accordance with an embodiment of the presentinvention, such an interventional device 100 is secured to the table orplatform of the scanner or imaging apparatus by affixing or mounting theinterventional device to a positioning apparatus 400 as is known tothose skilled in that art, such as that illustrated in FIG. 2. Thepositioning apparatus 400 is any of a number of devices or apparatusesthat provide a mechanism for flexible initial positioning of theinterventional device 100 as well as securing the interventional deviceto the table/platform.

The illustrative positioning apparatus 400 includes a slide member 410,a sliding mount 402 and a support arm 404. The slide member 410 isaffixed or secured to the table, bed or platform of the scanner orimaging apparatus. The support arm 404, which in an exemplary embodimentcomprises a snake mount, is secured to the sliding mount 402 and to theinterventional device positioning stage 200. The sliding mount 402 isslidably disposed or mounted upon the slide member and is configuredwith a locking mechanism that allows the slide mount to be selectivelylocked to and unlocked from the slide member.

Such an interventional device 100 includes an end-effector 150, apositioning stage 200, an insertion stage 250 and actuation shafts 300a,b that are operably coupled to the positioning device and theinsertion device. Although described in more detail hereinafter, ingeneral terms; the end-effector 150 is introduced into a natural cavityin a subject (e.g., mammalian body), such as for example a rectum oruterus, or an artificial cavity formed in the body such as for exampleusing laparoscopic type of procedures. The positioning stage 200 or themotion stage is operably coupled to the end-effector 150 and providestranslation and/or rotation for the end-effector. The insertion stage250 is operably coupled to the end-effector 150 so as to control theinsertion of a medical device such as a needle into the tissues of thetarget site (e.g., target tissues) such as for example the prostate andits retraction therefrom. The actuation shafts 300 a,b are operablycoupled to the insertion stage 250 and the positioning stage 200respectively in such a manner so as to allow for remote operation of theinterventional device 100, more particularly the remote operation ofeach of the insertion stage 250 and the positioning stage 200, from alocation that is outside the confines of the scanner/imaging device aswell as being outside the field of view of the scanner/imaging device.

It should be recognized that while the interventional device 100 isillustrated with an in seriatim ordering of the end-effector 150,positioning stage 200 and the insertion stage 250, this shall not beconsidered a limitation on the present invention as it is within theskill of any of those knowledgeable in the art to arrange and configurethe interventional device so the insertion stage is disposed between thepositioning stage and the end-effector as well as arranging theinsertion stage so as to be functionally in parallel with thepositioning stage.

Referring now to FIGS. 4-6, there is shown various views of anend-effector 150 according to an embodiment of the present inventionthat includes a sheath 152 and a medical device or needle carrier 154that is disposed within an interior compartment 160 of the sheath. Also,the device/needle carrier 154 is disposed within the sheath interiorcompartment 160 so as to be rotatable and/or translatable along the longaxis therein. In an exemplary embodiment, the device/needle carrier 154is a substantially cylindrical member. In the following discussion thedevice/needle carrier 154 is referred to as the needle carrier forsimplicity, however, this shall not be construed as narrowing the scopeof the present invention to this specific example.

The sheath 152 is configured and arranged so as to form a relativelyrigid member that minimizes deformation and displacement of the organduring positioning (i.e., during rotation or translation) of the needlecarrier 154 and to maintain a generally stationary position with respectto the organ of interest/target tissues when the interventional deviceis in use (e.g., imaging tissue, inserting needle into tissue, etc.). Inthe illustrated embodiment, the sheath 152 is in a non-moving relationwith respect to the positioning stage 200. In other embodiments, asdescribed hereinafter, the sheath is arranged so as to be moveable withrespect to the positioning stage 200 (e.g., rotated with respect to thepositioning stage and about a long axis of the sheath).

The sheath 152 also is configured so as to include a small window orthrough aperture 162, which through aperture extends partially about thecircumference of the sheath and partially axially along the length ofthe sheath. In particular exemplary embodiments, the through aperture162 is located in a portion of the sheath proximal a distal end of thesheath that is inserted into the natural or artificial body cavity. Inanother embodiment, the through aperture 162 or window is formed in anend surface of the sheath 152.

It also is within the scope of the present invention, and yet anotherembodiment, for the sheath to be configured and arranged without athrough aperture or window. In this embodiment, an area or region of thesheath 152 is designated as an area (hereinafter penetration area) inwhich the needle 350 penetrates through or pierces a wall (e.g., a sideor end wall) of the sheath 152 as the needle is deployed from thecarrier member through the exit port 175 to the target site. In furtherembodiments, the sheath 152, more particularly the penetration area ofthe sheath, is configured and arranged to facilitate such penetration orpiercing by the needle 350. For example, the wall thickness of thesheath 152 in the penetration area is reduced, thereby reducing theforce required to be developed for penetration or piercing.

The window or through aperture 162 or the penetration area is configuredand sized so as to accommodate a predetermined amount of rotation andtranslation movement by the needle carrier 154 to locally adjust theexit port 175 for the needle 350 exiting the end-effector 150 withrespect to the target site in the target tissues. In the case where theinterventional device includes a plurality of guide channels 174 a,b,the window or through aperture 162 or the penetration area is configuredand sized so as to accommodate a predetermined amount of rotation andtranslation movement by the needle carrier 154 to locally adjust theexit ports 175 a,b for the needle 350 exiting the end-effector 150 withrespect to the target site in the target tissues. This provides amechanism for fine-tuning the location of the needle carrier exit port175 with respect to the target site without requiring the re-positioningof the sheath 152 in the natural or artificial body cavity. As describedherein, the needle 350 exits from the exit port 175 of the needlecarrier 154 and passes through the through aperture 162 and thencethrough the tissues until the end of the needle is positioned at thetarget site. In the case where the sheath is rotatable with respect tothe positioning stage 200 as described herein, the configuration andsize of the window or through aperture 162 or the penetration area canbe reduced in comparison to that described above when the sheath is infixed relation to the positioning stage 200.

In a further embodiment, the sheath further includes a second window orthrough aperture 163 in which is received an extension member 172 forone of the tracking coils 170 c. The second window or through aperture163 is configured and sized so as to accommodate a predetermined amountof rotation and translation movement by the needle carrier 154 so thatthe rotational or translational motion of the extension member 172 doesnot cause the extension member to come into contact with the sides ofthe second through aperture 163.

Disposed in the sheath 152 and about the perimeter of the first throughaperture 162 is an MRI imaging loop antenna 164 that produces real-timeanatomic images stationary with respect to the subject anatomy. The MRimaging loop antenna 164 or coil antenna is so arranged such that thevolume of tissue that can be imaged by this antenna includes thepossible target sites of the needle when it is deployed from the needlecarrier 154 into the target tissues. The MRI imaging antenna 164 issized and otherwise configured as is known by those skilled in the MRarts so that the antenna can image the desired depth that includes theamount the needle can be deployed within the target tissues and with adesired SNR.

The needle guide or carrier 154 is configured and arranged so as toinclude therein a guide channel 174 that generally extends lengthwise orlongitudinally from a proximal end of the needle carrier 154 to theneedle exit port 175. In an exemplary embodiment, the guide channel is174 is sized and configured so as to movable receive therein a flexiblestandard MRI-compatible 18 G biopsy needle. The guide channel 174 can beformed in the structure comprising the needle carrier 154, be a tubularmember disposed, mounted/affixed or secured within the needle carrier(e.g., a plastic or Teflon tubular member) or be formed of a combinationof such structure and tubular members.

In a preferred embodiment, the needle exit port 175 is positioned in aside surface of the needle carrier 154, although other positions andorientations of the needle exit port 175 are contemplated for use withthe present invention, including a needle exit port that is positionedin an end surface of the needle carrier. In this way, the needle 350generally passes axially through the end-effector 152 via the channel174 but is re-directed by portions of the channel such that the needleexits through a surface of the needle carrier 154, including a side orend surface thereof, to enter the tissues or the body, for examplethrough the rectum wall when the target tissues are those of theprostate. Consequently, the configuration of the end-effector of thepresent invention allows the needle exit port 175 to be relativelyeasily positioned at an ideal location with respect to the targettissues in particular when compared or contrasted with the procedures ortechniques followed for conventional devices such as end-shot type ofdevices. Also, the configuration and methodology of the presentinvention provides a mechanism by which the needle can be successivelysteered or directed to a same tissue target location which as indicatedherein cannot be readily accomplished with conventional devices ortechniques particularly those that use manual manipulation.

In more particular embodiments, the guide channel 174 includes arcuateportions, in particular, the portion of the guide channel 174 thatintersects with a wall (e.g., sidewall) of the needle carrier 154 andthe needle exit port 175 forms a circular arc. The needle 350 exits thechannel 174 via the exit port 175 and follows a straight trajectorytangential to the arc at the point of exit. As also indicated herein,the needle can be rotated as it is being translated through the channeland exiting through the exit port. As explained herein, the angle formedbetween the needle and the wall (e.g., side or end wall) of the needlecarrier is determined using a calibration procedure/methodologyaccording to the present invention.

Referring now particularly to FIG. 5B, there is shown an end-effector150 a according to another embodiment of the present invention disposedwithin the rectum so as to target tissue of the prostrate. Such an endeffector 150 a includes a needle guide 154 a that is disposed with asheath 152 a, which needle guide is configured so as to include aplurality of guide channels 174 a,b and exit ports 175 a,b. As describedherein, in use the exit ports 175 a,b would be opposite to the window orthrough aperture 162 in the sheath 152 a.

In more particular embodiments, the plurality of guide channels 174 a,Bare arranged in the needle carrier 154 a, so that the exit ports foreach of the guide channels are displaced from each other along withrespect to one, two or three dimensions or directions so that theneedle(s) exiting the needle carrier can reach different parts of thetissue (e.g., different parts of the prostrate). In an illustrativeembodiment, the portions of the guide channels 174 a,b proximal therespective exit port are located in a single plane and so that they areat different angles with respect to a long axis of the needle carrier154 a, for example to form a 20 degree guide channel portion and a 30degree guide channel portion. This shall not be considered limiting asthe needle carrier can be configured with three or more guide channel,for example, three guide channels having 20, 27.5 and 35 degree channelportions respectively.

As also illustrated in FIG. 5B, the sheath 152 can be arranged toinclude one or more entrance ports or passages 153 a,b that are arrangedso that the other portions of the guide channels external to the needlecarrier 154 a pass through the sheath to the needle carrier 154 a.Preferably such ports or passages in the sheath are located so as to belocated external to the body cavity or the like in which is received theend effector.

In yet another alternative embodiment, and as discussed hereinafter, theportion of the guide channel 174 proximal the exit port 175 isconfigured and arranged so as to be flexible and moveable in at last onedirection and more particularly in three directions such that the guidechannel intersects different locations at least longitudinally and moreparticularly, angularly and/or longitudinally along the surface of theneedle carrier 154. For example, this portion of the guide channel 174can be in the form of a flexible tubular member. Also, any of a numberof mechanisms known to those skilled in the art is operably coupled tothe flexible portion to allow the exit port 175 to be selectivelyre-positioned via manual action or via a remote located device.

In further embodiments, the flexible portion of the guide channel 174and the mechanism that is operably coupled to the flexible portion areconfigured and arranged so as to control and adjust the exit angle ofthe needle 350 with respect to a wall or axis of the needle carrier 154.In this way, the needle 350 can be steered or directed to differenttarget areas without repositioning the exit port 175 or withoutre-positioning of the needle carrier.

In an illustrative exemplary embodiment, the needle carrier 154 iscomprised of two halves that are pinned or otherwise secured together.One half section of the exemplary needle carrier 154 is configured andarranged so as to carry the three registration coils 170 a-c thatcomprise active fiducials, providing the spatial position of the probein the MRI coordinate system. In this embodiment, two coils 170 a,b arepositioned along the main axes of the needle carrier 154 and the thirdcoil 170 c is positioned at a certain offset of the axes so as to allowregistering the rotation of the probe. Reference also shall be made toU.S. Pat. Nos. 5,271,400; 6,470,204 and 6,492,814 the teachings of whichare incorporated herein by reference for details as to such MRI activetracking coils. The other half section of the exemplary needle carrier154 is configured so as to include the guide channel 174 for guiding theneedle 350 to the exit port 175.

In more particular embodiments, one or more of the sections of theneedle carrier 154 is configured and arranged so as to include one ormore passive fiducial channels 171. A material that is appropriate forpassively visualizing using a given imaging technique is disposed in thepassive fiducial channels 171 or secured in an appropriate fashion toand/or within the carrier guide 154. For example, in the case of imagingtechniques embodying MRI techniques, a material comprising an MRIcontrast agent such as gadolinium is disposed in the fiducial channel171. This shall not be limiting as any of a number different kinds andtypes of passive fiducials can be located in the fiducial channel thatis appropriate for the external imaging technique being used to imagethe tissues and at least the end-effector 150 of the interventionaldevice 100 including that described further herein.

In further embodiments; the interventional device 100 further includes amechanism that is operably coupled to the needle, or to each needle whenthe interventional device is configured with a plurality of guidechannels 174 a,b, so as to rotate the needle about the long axisthereof; more particularly rotating about the long axis as the needle isbeing deployed from the needle carrier 154 to the tissues. Trials haverevealed that a needle 350 can be passed though significantly biggercurvatures (e.g., smaller radii of curvatures) by rotating the needle asit passes through a channel 174 with such curvatures while inserting itinto the tissues. This rotating insertion distributes elasticdeformation equally along a helical path in the needle, resulting in astraight trajectory for the needle. In other words, as the needle isadvanced through a needle passage, such as the carrier member channel174, with simultaneous rotation and translation, the needle will emergefrom the passage straight (i.e., with negligible curvature). In the casewhere the needle 350 is only being translated (i.e., without rotation)through a passage having a small radius of curvature; as the needlepasses through the needle passage inelastic bending deformation occursresulting in the needle emerging from the passage with a repeatablecurvature and thus following a non-linear trajectory. Alternatively,such significant curvatures can be used to direct the needle 350 as itexits the needle exit port 175 in a non-linear fashion to a target site.

The sheath 152 and needle carrier 154 are each constructed of any of anumber of materials known to those skilled in the art that arebio-compatible, appropriate for the intended use and are appropriate foruse with the particular imaging technique being utilized for imaging thetarget tissues. In more particular embodiments, the materials of thesheath 152 and needle carrier 154 are selected so as to minimize thecreation of unwanted image artifacts by these components. In exemplaryembodiments, the end-effector 150 including the sheath 152 and needlecarrier 154 are manufactured from any of a number of biocompatibleplastic materials having sufficient strength and rigiditycharacteristics for the intended use. The MRI loop 164 antenna and thetracking coils 170 a-c are made from copper wire or other acceptablematerial and the needle 350 is made of a material that preferably isnon-magnetic and resilient.

Referring now to FIGS. 8-9 there is shown a positioning stage 200according to one aspect of the present invention that provides therotation and the translation for the end-effector 150, more particularlythe rotation and translation of the needle carrier 154 within the sheath152. Such rotation and translational motion is communicated to theneedle carrier 154 via the main shaft 202 of the positioning stage. Themain shaft 202 is operably and mechanically coupled to the needlecarrier 154 using any of a number of mechanisms or techniques known tothose skilled in the art including the use of pins, screws and aninterference fit.

Two concentric shafts 300 b are operably coupled to the positioningstage 200 so as to transform rotation of one or more of these shaftsinto translation and/or rotation of the main shaft 202. In oneembodiment, the concentric shafts 300 b are manually actuated fromoutside the gantry of the imaging scanner. In another embodiment, theconcentric shafts 300 b are coupled to any of a number of drivemechanisms or motors, electrical or hydraulic, as is known to thoseskilled in the art for remote, selective, and controlled rotation of theconcentric shafts.

In exemplary embodiments, the concentric shafts 300 b are coupled so asto act over a gear reduction 203 a,b to turn two separate nuts 206, 210that are engaged with the main shaft 202. The rotation nut 206 connectsto the main shaft 202 through two splines 208 that run in a lineargroove of the shaft, providing the rotation of the main shaft. Thetranslation nut 210 is a threaded nut that engages threads of the mainshaft 202. Thus, rotation of the translation nut 210 thereby providesthe translation of the main shaft 202.

The positioning stage 200 also includes a housing 212 that in anillustrated embodiment includes a block and two lids. The housing 212rotatably supports the main shaft 202 and also restricts the rotationand translation nuts 206, 210 from translating which as is known tothose skilled in the art causes the main shaft to translate and/orrotate responsive to rotation of the respective nut(s). The housingblock also includes an attachment member that is secured to a universalmount such as that illustrated above in FIG. 2.

In one embodiment, the positioning stage 200 and the components thereofare constructed of any of a number of materials known to those skilledin the art that are appropriate for use with the particular imagingtechnique being utilized for imaging the tissues as well as beingappropriate for the intended use. In more particular embodiments, thematerials are selected so as to minimize the creation of unwanted imageartifacts by these components. In exemplary embodiments, the materialsinclude any of a number of plastics known to those in the art that areappropriate for the intended use (e.g., having sufficient strength andrigidity characteristics for the intended use).

In as much as the interventional device 100 is typically arranged sothat the positioning stage 200 is not in the field of view of themedical imaging apparatus; or is at least outside the first zone of theMRI imaging device, it is within the scope of the present invention thatin alternative embodiments other materials, for example non-magneticmaterials such as aluminum, brass, titanium and the like to be used forone or more of the components comprising the positioning stage. Forexample, the meshing gears comprising the gear reduction or therotational or translation nuts can be made of such non-magneticmaterials thereby allowing part sizes to be reduced because of thestrength characteristics of such materials as compared to typicalmedical grade plastics.

Referring now to FIGS. 10-11 there is shown various views andembodiments of an insertion stage 250 according to the presentinvention. As indicated above, the needle insertion stage 250 isconfigured and arranged so as to deploy the needle from the needlecarrier 154 and to insert the needle to a predetermined depth in thetissues and also to retract the needle from the tissues after completingthe biopsy or treatment process. The insertion stage 250 transformsrotation of a knob affixed to another actuation shaft 300 a into awell-defined insertion of the needle 350 to a pre-determined targetdepth and also actuates the shooting mechanism of a biopsy gun. In anexemplary embodiment, a 18 G standard prostate biopsy needle (Daum Gmbh,Schwerin, Germany) was adapted for use.

The knob turns a lead screw 252 that engages a thread in a block 254 ofthe insertion stage 250. The coupling transfers movement of the screwinto the cartridge 260, which runs in a pocket of the block and carriesthe biopsy gun 262. Switching between a round cartridge 260 a (FIG. 10A)or a square cartridge 260 b (FIG. 10B) and tightening or loosening asetscrew on the coupling 273 allows for either a rotating insertion or apure translating insertion of the needle 350. As indicated above,rotating insertion allows a needle to be passed through significantlylarger curvatures than in the case where non-rotating insertion isperformed. In addition, some studies have indicated that rotatinginsertion also assists the needle in penetrating the tissues at theentrance site and within the body thereby minimizing or reducing insult(see also US Patent Publication No. 2002/0111634, the teaching of whichare incorporated herein by reference). Such reduction is particularlyadvantageous in cases where multiple needle insertions are contemplated.In the case where the insertion stage 250 is configured to performbiopsy, a push-pull plunger 263 actuates the biopsy gun 262 by loadingand firing the gun.

In other embodiments, the insertion stage is configured and arranged soas to allow access to the proximal end of the needle 350 that is locatedoutside of the subject. In use, the user can insert any of a number ofmedical devices, therapeutic mediums or compositions, imaging devicesand the like through the lumen of the needle 350 and into the targetsite of the target tissues. For example, a loopless MRI imaging antennacan be passed along the length of the needle so as to more directlyimage the tissues at or about the target site.

Markers or seeds can be passed though the needle lumen and depositedwithin the tissues at or about a target site to facilitate localizationof the tissues within target site. Thus, and for example, medicalpersonnel can use such markers or seeds to provide a more accuratelyidentified location for therapeutic treatment for example by a beamtherapy technique. Such seeds or markers themselves also can comprise asource of radiotherapy as well as devices that provide long-term andcontrolled release of therapeutic compounds of chemotherapeutic agentsto the tissues. The foregoing is illustrative of a few medicaltechniques and procedures that can be used in combination with theinterventional device 100 of the present invention so as to providediagnostic and/or therapeutic treatment.

Because such materials, agents and medical devices are introducedoutside the field of view of the imaging apparatus, the medicalpersonnel need not have significant access to the bore of the mainmagnet. Also, because the medical devices and the like are not presentwithin the field of view while imaging the tissues before treatment themedical devices and the like do not present a concern with thegeneration of a problematic image artifact. Finally, the medical deviceand the like can be configured and arranged so that it can be imagedusing the desired imaging technique (e.g., MRI) after the medical deviceor the like have been inserted or localized to the target site of thetarget tissues.

In the case where therapeutic agents are to be administered to thetissues or cells at or about the target site, the insertion stage 200can include a syringe, a syringe pump or other mechanism or device knownto those skilled in that art that is fluidly coupled to the proximal endof the needle 350. In use, the therapeutic medium or other fluid isthereby injected through the needle lumen 350 by such syringe, syringepump or other such mechanism or device.

In one embodiment of the present invention, the insertion stage 250,more particularly the components thereof except the push-pull plunger263 are made from a material that is appropriate for the imaging processand for not creating image artifacts. In an exemplary embodiment, whenMRI comprises the imaging technique, the insertion stage 250 includingthe constituents thereof except for the push-pull plunger, and themedical devices, delivery devices and the like coupled to the proximalend of the needle, are made from plastics. In an illustrativeembodiment, the push-pull plunger is made from aluminum or othernon-magnetic materials when MRI is the imaging technique. The push-pullplunger 263 is located sufficiently far from the field of view of theimaging apparatus so as to not cause a measurable signal distortion. Inas much as the interventional device 100 is typically arranged so thatthe insertion stage 250 is not in the field of view of the medicalimaging apparatus; it is within the scope of the present invention forother materials, for example non-magnetic materials such as aluminum,brass, titanium and the like to be used for one or more of thecomponents comprising the insertion stage.

Referring now to FIGS. 12-13 there is shown an interventional device 500according to another aspect of the present invention that is secured toanother illustrative positioning apparatus 600. The illustratedpositioning apparatus 600 includes a plurality of segments 602 that areinterconnected to each other by one of a plurality articulated joints604. The articulated joints 604 are of the type that can be selectivelyloosened and tightened for example by the tightening of a screw or bolt.One of the segments 602 is connected to a slide mount 402 and another ofthe segments 602 is in connected to the interventional devicepositioning stage. Reference shall be made to the discussion above forFIG. 2 as to further details for the slide mount 402 and the slidemember 410. As is known to those skilled in the art, the plurality ofsegments 602 and articulated joints 604 in combination with the slidingmount 402 and the slide member 410 of the positioning apparatus 600provide a mechanism for flexible initial positioning of theinterventional device 500 as well as securing the interventional deviceto the table, bed or platform of the scanner or imaging apparatus.

The interventional device 500 includes an end-effector 520, apositioning stage 550 and an insertion device 250, where reference shallbe made to the above discussion regarding FIGS. 4-7 and 10-11 forfurther details of the insertion device and the end-effector nototherwise provided below. In this embodiment, the end-effector 550differs from that described above in that the within embodiment does notinclude an extension member 172 that extends outside of the sheath 552and the internally located components of the needle carrier 554 havebeen arranged so as to reduce the cross-section of the sheath and theneedle carrier.

The positioning stage 550 of this embodiment includes two flexibleshafts 570 a,b that have actuation elements (e.g., knobs, motors, andthe like) that are located remote from the field of view of the imagingapparatus. The flexible shaft 570 a for controlling translation motionof the needle carrier is coupled to a nut 572 via gear reduction 574such that rotation of the flexible shaft in turn causes the nut torotate over a gear reduction 574. The nut 572 is threaded and threadablyengages the main shaft 552, which is threaded. Thus, as the nut 572rotates, such rotation drives the main shaft in a translational motion.

The other flexible shaft 570 b is connected to a small gear 575, whichengages an internal gear 576. The internal gear 576 is held stationaryby the housing of the positioning stage 550. Consequently, rotation ofthe small gear 575 causes the entire inner assembly including theactuation shafts 570 a,b and the main shaft 552 to rotate.

In the foregoing discussion, the mechanisms and methods described fortracking the rotational and/or translational movement of the needlecarrier uses an external imaging apparatus for locating the trackingdevices. It is within the scope of the present invention for aninterventional device according to the present invention to embody anyof a number of positional tracking devices, apparatuses, systems andmethods as is known to those skilled in the art. In an exemplaryembodiment, and with reference to FIG. 13A, there is shown a portion ofa positioning stage 550 of FIG. 12 including any one of a number ofdevices known to those skilled in the art, that allow a position to bedetermined, such devices include optical encoders, incremental encoders,position encoders and potentiometers.

In the illustrated embodiment, a positioning encoder 577 is positionedor mounted to the housing 555 of the positioning stage proximal the nut572 that causes translation motion of the main shaft 552. Thepositioning encoder is configured and arranged so as to measure therotation of the translation nut 572, and thus provide an output signalrepresentative of the translation of main shaft 552. In an exemplaryembodiment the positioning encoder is an optical encoder or apotentiometer. In this way, the amount of rotation of the translationnut 572 can be equated to amount of translation of the main shaft 552and thus an amount of translation of the carrier member 154. Thepositioning encoder 577 or encoder device is operably coupled via acable 579 to instrumentation and/or devices positioned external to thefield of view of the imaging apparatus that provide a remote indicationto the user of the amount of translation.

Similarly, a positioning encoder or other position determining devicecan be placed within the positioning stage housing 555 and appropriatelypositioned so as to measure the rotation of the main shaft 552. Further,the needle 350 can be configured so as to include a mechanism, forexample a code strip affixed to the needle that could be used inconjunction with an encoding or position determining device to determinean amount of translation of the needle and thereby an amount ofinsertion of the needle into the tissues. Reference also should be madeto the discussion hereinafter describing embodiments and/or aspects ofother interventional device of the present invention configured with arotating sheath. As also described hereinafter, in other aspects of thepresent invention the interventional device can embody a hybrid trackingmethodology. As such, it is within the scope of the present inventionfor any of the interventional devices described herein to be adapted soas to embody any of the tracking methodologies and systems/devicesdescribed herein.

Reference also should be made to the foregoing discussion as to FIGS.1-11 as to the positioning stage, the insertion stage and theend-effector as to the materials and other construction details.

In the interventional devices 100, 500 hereinabove described, afterinsertion of the end-effector into the subject, the target tissues areimaged using an MRI imaging loop antenna or coil 164. Referring now toFIG. 14, there is shown an end-effector 700 according to another aspectof the present invention that can be used in combination with thepositioning stages 200, 550 or the insertion stage 250 as describedherein.

The end-effector 700 includes a sheath 702 and a medical device orneedle carrier 704 that is disposed within an interior compartment 730of the sheath. Also, the device/needle carrier 704 is disposed withinthe sheath interior compartment 730 so as to be rotatable and/ortranslatable along the long axis therein. In an exemplary embodiment,the device/needle carrier 704 is a substantially cylindrical member. Inthe following discussion the device/needle carrier 704 is referred to asthe needle carrier for simplicity, however, this shall not be construedas narrowing the scope of the present invention to this specificexample.

The sheath 702 is configured and arranged so as to form a relativelyrigid member that minimizes the deformation and displacement of theorgan during positioning (i.e., during rotation or translation) of theneedle carrier 704 probe and to maintain a generally stationary positionwith respect to the organ of interest/target tissues. The sheath 702also is configured so as to include a small window or through aperture710, which through aperture extends partially about the circumference ofthe sheath and partially axially along the lengthwise of the sheath. Inparticular exemplary embodiments, the through aperture 710 is located ina portion of the sheath proximal a distal end of the sheath that isinserted into the natural or artificial body cavity. As also indicatedherein, in further embodiments, the sheath 702 can be configured andarranged so as to include a penetration area or penetration regioninstead of the through aperture 710.

The window or through aperture 710 or the penetration area is configuredand sized so as to accommodate a predetermined amount of rotation andtranslation movement by the needle carrier 704 to locally adjust theexit port 725 entrance site for the needle 350 exiting the end-effector700 with respect to the target site in to the target tissues. Thisprovides a mechanism for fine tuning the location of the needle carrierexit port 725 with respect to the target site without requiring there-positioning of the sheath 702 in the natural or artificial bodycavity. As described herein, the needle 350 exits from the exit port 725of the needle carrier 704 and passes through the through aperture 710and thence through the tissues until the end of the needle is positionedat the target site.

The needle guide or carrier 154 is configured and arranged so as toinclude therein a guide channel 724 that generally extends lengthwise orlongitudinally from a proximal end of the needle carrier 704 to theneedle exit port 725. In an exemplary embodiment, the guide channel is724 is sized and configured so as to movable receive therein a flexiblestandard needle. The guide channel 724 can be formed in the structurecomprising the needle carrier 704, be a tubular member disposed,mounted/affixed or secured within the needle carrier (e.g., a plastic orTeflon tubular member) or be formed of a combination of such structureand tubular members.

In a preferred embodiment, the needle exit port 725 is positioned in aside surface of the needle carrier 704, although other positions andorientations of the needle exit port 725 are contemplated for use withthe present invention, including a needle exit port positioned in an endsurface of the needle carrier 704. The needle 350 generally passesaxially through the end-effector 700 via the channel 724 but isre-directed by portions of the channel such that the needle exitsthrough a surface, a side or end surface, of the needle carrier 704 toand finally enters the tissues or the body, for example through therectum wall when the target tissues are those of the prostate.Consequently, the configuration of the end-effector 700 of the presentinvention allows the needle exit port 725 to be relatively easilypositioned at an ideal location with respect to the target tissues inparticular when compared or contrasted with the procedures or techniquesfollowed for conventional devices such as end-shot type of devices.Also, the configuration and methodology of the present inventionprovides a mechanism by which the needle can be successively, steered ordirected to a same tissue target location which as indicated hereincannot be readily accomplished with conventional devices or techniquesparticularly those that use manual manipulation.

In more particular embodiments, the guide channel 724 includes arcuateportions, in particular, the portion of the guide channel 724 thatintersects with the sidewall of the needle carrier 704 and the needleexit port 725 forms a circular arc. The needle 350 exits the channel 724via the exit port 725 and follows a straight trajectory tangential tothe arc at the point of exit. As also indicated herein, the needle 350can be rotated concurrent with translation through the channel. Asexplained herein, after assembly of the needle carrier, the angle formedbetween the needle and sidewall of the needle carrier is determinedusing a calibration procedure/methodology according to the presentinvention. As indicated herein, it also is contemplated and thus withinthe scope of this embodiment, for the end-effector 700 to be arranged soas include a plurality of guide channels.

In an alternative embodiment, the portion of the guide channel 724proximal the exit port 725 is configured and arranged so as to beflexible and moveable in at last one direction and more particularly inthree directions such that the guide channel intersects differentlocations at least longitudinally and more particularly, angularlyand/or longitudinally along the side surface of the needle carrier 704.For example, this portion of the guide channel 724 can be in the form ofa flexible tubular member. Also, any of a number of mechanisms known tothose skilled in the art is operably coupled to the flexible portion toallow the exit port 725 to be selectively re-positioned via manualaction or via a remote located device.

In further embodiments, the flexible portion of the guide channel 174and the mechanism that is operably coupled to the flexible portion areconfigured and arranged so as to control and adjust the exit angle ofthe needle 350 with respect to a wall or axis of the needle carrier 154.In this way, the needle 350 can be steered or directed to differenttarget areas without repositioning the exit port 175 or withoutre-positioning of the needle carrier.

The needle carrier 704 also is configured and arranged so as to includean ultrasound crystal 720 that is arranged so as to image a volume oftissues that includes the tissues of the target site and the tissues inwhich the needle would be disposed if deployed from the needle carrierin a given position. The ultrasound crystal is any of a number ofultrasound crystals known in the art and appropriate for the intendeduse, including those crystals and devices embodying crystals such asthose used in connection with transrectal ultrasound guided needlebiopsy and low permanent seed brachytherapy procedures.

The sheath 702 and needle carrier 704 are each constructed of any of anumber of materials known to those skilled in the art that arebio-compatible, appropriate for the intended use and are appropriate foruse with the particular imaging technique being utilized for imaging thetarget tissues. In more particular embodiments, the materials of thesheath 702 and needle carrier 704 are selected so as to minimize thecreation of unwanted image artifacts by these components. In exemplaryembodiments, the end-effector 700 including the sheath 702 and needlecarrier 704 are manufactured from any of a number of a biocompatibleplastic materials having sufficient strength and rigiditycharacteristics for the intended use.

Although the mechanism for imaging the tissues of the target site afteran interventional device including an end-effector 700 according to thisaspect of the present invention is ultrasound, it is within the scope ofthe present invention for other imaging techniques, including CT and MRItechniques to be used, to determine the initial position of theinterventional device as well as any imaging occurring concurrent withand following post treatment or diagnostic procedures. As such, it iswithin the scope of the present invention for the needle carrier 704according to this aspect of the present invention to include passiveand/or active fiducials to assist such other imaging systems in imagingand determining the location of the end-effector within the subject orbody.

Referring now to FIG. 26 there is shown a perspective view of aninterventional device 800 according to another aspect of the presentinvention. Such an interventional device 800 includes an end-effector850, a positioning stage 820, and an insertion stage 840. Such aninterventional device 800 also can further include mechanisms (not shownin FIG. 26) that are operably coupled to the positioning stage and/orthe insertion stage so as to cause these stages to perform the movingfunctions described herein.

The positioning stage 820 or the motion stage is operably coupled to theend-effector 850 and provides translation and/or rotation for theend-effector. As described hereinabove, the insertion stage is operablycoupled to an inner member 854 so as to control the insertion of amedical device such as a needle into the tissues of the target site(e.g., target tissues) such as for example the prostate and itsretraction therefrom. Reference shall be made to the foregoingdiscussion for FIGS. 1-11 for details of the interventional device nototherwise described below. While the following describes a number offeatures, this shall not be considered limiting. It is within the scopeof the present invention that an interventional device can selectivelyembody one or more of the below described features.

The end-effector 850 includes a sheath 852 and an inner member 854 thatis disposed within an interior compartment of the sheath. Also, theinner member 854 is disposed within the sheath interior compartment soas to be rotatable and/or translatable along the long axis therein. Inan exemplary embodiment, the inner member 154 is a substantiallycylindrical member (e.g., rod like).

The sheath 852 is configured so as to be generally cylindrical in shape.The sheath also is moveably connected to the positioning stage 820 sothe sheath is rotatable with respect to or about a long axis of thesheath. In interventional devices described above for FIGS. 1-14, thesheath 150 is stationary during the procedure as a stationary sheathprevents organ deformation during translation and rotation of the needleguide. For a sheath that is cylindrical in shape, rotation of the sheathdoes not result in organ deformation since it just rotates within theopening (e.g., rectum). This is particularly advantageous as the windowor through aperture 162 (see FIGS. 4, 5A) can be reduced in size ascompared to the one for an interventional device having a fixed sheath.In more specific embodiments, the window or through aperture (e.g.,cutout) for a sheath 852 that is rotatable, can be configured andarranged as a slot instead of the bigger window described above.

As indicated above, the sheath 852 is moveable coupled or connected tothe positioning stage 820, more particularly, the sheath is operablycoupled to a drive mechanism 822 so that movement of the drive mechanismcauses the sheath 852 to rotate as described herein. In particularembodiments, the drive mechanism 822 is a drive wheel or knob, whererotation of the drive wheel causes the sheath to rotate. In furtherembodiments, the positioning stage 820 includes a positioning encoder824 that is operably coupled to the drive mechanism 822 or the sheath852 so that a signal is outputted from the positioning encoder that isrepresentative of the rotational movement of the sheath. Such anpositioning encoder 824 is an of a number of such devices known to thoseskilled in the art and includes electrical, optical, electro-optical ormechanical position encoders.

The inner member 854 is moveable coupled or connected to the insertionstage 840, more particularly, the inner member is operably coupled to adrive mechanism 844 so that movement of the drive mechanism causes theinner member to rotate within the sheath as described herein. Inparticular embodiments, the drive mechanism 842 is a drive wheel orknob, where rotation of the drive wheel causes the inner member 854 torotate. In further embodiments, the insertion stage 840 includes apositioning encoder 844 that is operably coupled to the drive mechanism842 or the inner member 854 so that a signal is outputted from thepositioning encoder that is representative of the rotational movement ofthe sheath. Such an positioning encoder 844 is an of a number of suchdevices known to those skilled in the art and includes electrical,optical, electro-optical or mechanical position encoders.

In further embodiments/aspects the interventional device 800 isconfigured so as to include a needle channel 864 that can be steered ormoved in one or more directions. Stated another way, the interventionaldevice 800 includes a mechanism that moves the needle channel 864 so asto thereby cause the needle 350 to exit the inner member 854 at one of anumber angles with respect to the long axis of the inner member (i.e.,mechanism changes angle of portion of the needle channel proximal theexit port in either one plane or three dimensionally). In this way,instead of having a number of needle channels such as shown in FIG. 5B,a single needle channel 864 with continuously varying angle is capableof reaching all parts of the tissue being targeted (e.g., the prostate).For example, prior to the interventional procedure being performed, theneedle guide 864 is positioned such that the entry hole in the sheath isplaced close to the anus of the patient. Since the entry of the needlechannel is thus positioned close to the anus of the patient, the angleof the needle channel 864 is maximized for all needle trajectories totargets in the prostate. It should be noted that steeper angles areexpected to result in less prostate deformation during the insertion ofthe needle.

There also is shown in FIG. 26 one illustrative example of a mechanismfor steering an in-plane steerable needle channel. In the illustratedembodiment, the needle channel 864 is rotated about a hinge 855 by theturning of the drive wheel 842 for controlling the needle angle. Thedrive wheel 842 cause the inner member 854 having a helical cut torotate. The helical cut is engaged with the needle channel 864, so thatrotation of the inner member 854 thereby results in a change in angle ofthe needle channel.

It should be recognized that it is within the scope of the presentinvention for the above-described interventional device to be configuredso as to include a plurality of needle channels as described above inconnection with FIG. 5B.

The interventional device according to this aspect also is configured soas to include a plurality of fiducials 871 a-d. In the illustratedembodiment, there are two passive fiducial marker tubes 871 a,bincorporated into the main axis of the interventional device and twofiducial marker tubes 871 c,d placed parallel to the needle channel.These fiducials 871 a-d and the position encoders 824,844 are utilizedin combination with a hybrid tracking methodology of the presentinvention as described hereinafter to determine the location of theimaging mechanism embodied in the end-effector as well as the locationof the end-effector. It should be recognized, that is within the scopeof the present invention to adapt the tracking method andfunctionalities (e.g., tracking coils) described above in connectionwith FIGS. 1-11 so as to be embodied with the interventional deviceaccording to this aspect of the present invention.

Referring now to FIG. 27 there is shown a perspective view of anotherinterventional device 900 according to another aspect of the presentinvention. Such an interventional device 900 includes an end-effector950, a positioning stage 920, and an insertion stage 940. Such aninterventional device 900 also can further include mechanisms (not shownin FIG. 27) that are operably coupled to the positioning stage and/orthe insertion stage so as to cause these stages to perform the movingfunctions described herein.

The positioning stage 920 or the motion stage is operably coupled to theend-effector 950 and provides translation and/or rotation for theend-effector. As described herein, the insertion stage 940 is operablycoupled to an inner member 954 so as to control the insertion of amedical device such as a needle into the tissues of the target site(e.g., target tissues) such as for example the prostate and itsretraction therefrom. Reference shall be made to the foregoingdiscussion for FIGS. 1-11 and FIG. 26 for details of the interventionaldevice not otherwise described below. While the following describes anumber of features, this shall not be considered limiting. It is withinthe scope of the present invention that an interventional device canselectively embody one or more of the below described features.

The end-effector 950 includes a sheath 952 and an inner member 954 thatis disposed within an interior compartment of the sheath and is coupledto the sheath, for example coupled by a key 953. The inner member 954 iscoupled or connected to the sheath 952 using any of a number oftechniques known to those skilled in the art so that the inner member isrotated by the rotation of the sheath. In an illustrative embodiment,the inner member 854 is coupled to the sheath using a key structure 953as is known to those skilled in the art. The inner member 954 also isdisposed in the sheath interior compartment so as to be translatablealong the long axis therein. In an exemplary embodiment, the innermember 954 is a substantially cylindrical member (e.g., rod like).

As with the sheath 854 described above, the sheath 952 according to thisaspect is configured so as to be generally cylindrical in shape. Thesheath also is moveably connected to the positioning stage 920 so thesheath is rotatable with respect to or about a long axis of the sheath.In more specific embodiments, the window or through aperture (e.g.,cutout) for the sheath 952 is configured and arranged as a slot.

As indicated above, the sheath 852 is moveable coupled or connected tothe positioning stage 920, more particularly, the sheath is operablycoupled to a drive mechanism 922 so that movement of the drive mechanismcauses the sheath 952 and thus also the inner member 954 to rotate asdescribed herein. In particular embodiments, the drive mechanism 922 isa drive wheel or knob. In further embodiments, the positioning stage 920includes a positioning encoder 924 that is operably coupled to the drivemechanism 922 or the sheath 952 so that a signal is outputted from thepositioning encoder that is representative of the rotational movement ofthe sheath.

The inner member 954 is moveable coupled or connected to the insertionstage 940, more particularly, the inner member is operably coupled to adrive mechanism 944 so that movement of the drive mechanism causes theinner member to translate within the sheath as described herein. Inparticular embodiments, the drive mechanism 942 is a drive wheel orknob. In further embodiments, the insertion stage 940 includes apositioning encoder 944 that is operably coupled to the drive mechanism942 or the inner member 954 so that a signal is outputted from thepositioning encoder that is representative of the rotational movement ofthe sheath.

In further embodiments/aspects the interventional device 900 isconfigured so as to include a needle channel 964 that can be steered ormoved in one direction. Stated another way, the interventional device900 includes a mechanism that moves the needle channel 964 so as tothereby cause the needle 350 to exit the inner member 954 at one of anumber angles with respect to the long axis of the inner member (i.e.,mechanism changes angle of portion of the needle channel proximal theexit port in a plane. In this way, instead of having a number of needlechannels such as shown in FIG. 5B, a single needle channel 964 withcontinuously varying angle is capable of reaching all parts of thetissue being targeted (e.g., the prostate).

There also is shown in FIG. 27 one illustrative example of a mechanismfor steering an in-plane steerable needle channel 964. In theillustrated embodiment, the needle channel 964 is rotated about a hinge955 by the turning of the drive wheel 942 for controlling the needleangle. As indicated above, rotation of the drive wheel 942 causes theinner member 954 to move axially within the sheath interior compartment,thereby changing the location of the exit of the needle channel 964 andthus also change the angle of the needle channel.

It should be recognized that it is within the scope of the presentinvention for the above-described interventional device to be configuredso as to include a plurality of needle channels as described above inconnection with FIG. 5B.

The interventional device according to this aspect includes a pluralityof fiducials 871 a-d as described above in connection with FIG. 26. Asindicated above, it also is within the scope of the present invention toadapt the tracking method and functionalities (e.g., tracking coils)described above in connection with FIGS. 1-11 so as to be embodied withthe interventional device 900 according to this aspect of the presentinvention.

Referring now to FIG. 28, there is shown a perspective view of anend-effector 990 according to another aspect of the present invention.Such an end-effector 990 includes a sheath 992 and an stabilizingmechanism 996 affixed to the sheath to stabilize the tissue beingtargeted (e.g., prostate) during insertion of needles. While thefollowing discussion refers to the prostrate, this is done forsimplicity and thus should not be considered as limiting the presentinvention to this illustrative embodiment.

In an embodiment, after the sheath 992 is inserted into the body opening(e.g., in the rectum of the patient), the geometry of the sheath ineffect is changed by the stabilizing mechanism 996 so as to thereafterstabilize the prostate during insertion of needles. In particularembodiments, the stabilizing mechanism 996 includes an inflatableballoon disposed about at least a significant portion of the sheath 992and which acts like a cradle for the prostate. In this embodiment, theinflatable balloon includes an opening therein so that needles can beinserted into the prostate through the inner, open part of the balloon.

In further embodiments, the MR imaging coil 164 is incorporated into theinflatable balloon. As the signal to noise ratio depends on the diameterof the imaging coil, an imaging coil in the inflated balloon provides animproved signal level over a rigid imaging coil design. In yet furtherembodiments, such an MRI imaging coil is arranged so as to expandoutwardly responsive to inflation of the balloon so that the imagingcoil is capable of imaging a larger volume than when it is affixeddirectly to the sheath.

The balloon is selectively interconnected to one of a fluid source and afluid discharge via interconnecting tubing and valves (not shown). Inuse, the balloon is fluidly coupled to the fluid source when the balloonis to be inflated and fluidly coupled to the fluid discharge when theballoon is top be deflated. It also is contemplated that the stabilizingmechanism can embody an actuatable mechanism (e.g., spring loadedmechanism) that is configured and arranged so that when the actuatablemechanism is actuated it causes the stabilizing mechanism to be deployedto contact the tissue.

In yet further embodiments, the stabilizing mechanism 996 comprises afoam layer that is affixed to the sheath. This foam layer appliesadditional pressure to the rectal wall to reduce motion of the prostate.

Referring now to FIGS. 29A-C there are shown various views of apositioning system 1200 according to another aspect of the presentinvention that is used to position any of the interventional devicesdescribed herein. To simplify the following discussion, reference ismade to the interventional device 900 shown in FIG. 27 and insertion ofthe end effector 950 for same into a rectum. This shall not beconsidered as limiting the positioning system of the present inventionto that illustrated in FIGS. 30A-C or to that use specifically describedherein. The positioning system includes a linear slide 1210 attached ona support-board 1202 and an arm 1220.

The positioning system 1200 of the present invention provides a flexibleinitial positioning of the interventional device 900 and a safe andrigid attachment for this to the support-board 1202. The positioningsecuring procedure has two steps. The first step comprises a manuallycoarse positioning of the whole system concurrently with the insertionof the end effector 950 into the patient rectum. At the end of thisphase the linear slide 1210 is locked with a locking mechanism as isknown to those skilled in the art. The second step comprises a manuallyfine adjustment of the probe position inside of the patient rectum.After that the arm 1220 is locked with a locking mechanism as describedfurther herein. This procedure is MRI-compatible and provides six degreeof freedom (DOF) in a limited range of motion, to have a lockingmechanism for all DOF, safe, easy, and fast, to be rigid enough to avoidthe breaks and/or the extra large elastic deflections.

The arm 1220 includes three links or segments, a base segment, 1230, anintermediate segment 1232, and a top segment 1234. The base andintermediate segments are connected through a spherical joint 1240 andthe top and intermediate segments are connected through anotherspherical joint 1242. Also, the base segment 1230 is operably coupled(e.g., attached) to the slide 1210 and the top segment is operablycoupled (e.g., attached) to the interventional device 900. In anillustrative embodiment, the spherical joints are ball-socket type ofspherical joints. Because the spherical joints 1240, 1242, individuallyprovide 3 DOF (i.e., 3 rotations), the top segment 1234 has 6 DOF (3translations and 3 rotations) relatively to the base segment 1230. Themotion range for each DOF depends on segments constructive shape anddimensions.

The locking mechanism 1260 includes pressure plates 1262 a,b, a screw1264, prism blocks 1266, pins 1268, and a handle 1270 including a handlenut 1272. In more particular embodiments, the locking mechanism 1260 isarranged so as to simultaneously eliminate the play in the sphericaljoints 1240, 1242 and to generate a pressure between each ball and itssocket of a spherical joint that will generate a friction force (torque)greater than the active force (torque) applied on the segments.

By tightening the helical joint comprising the screw 1264 and handle-nut1272 an axial force is created that in effect presses the pressureplates 1262 a,b against each other. As the pins 1268 and the prismblocks 1266 are located between the pressure plates 1262 a-b, the forceis transmitted in a perpendicular direction, through the rods 1280 ofthe intermediate section 1232, to the sockets and thus developing thenecessary pressure in the contact with the balls. The reactive forceswork through the case and fixed sockets.

Such an arm 1220 of the positioning system 1200 makes it possible tomount the interventional device 900 in any of a prone, supine ordecubitus positions. Also, the mounting allows the interventional device900 to be oriented in arbitrary angle along the scanner's long axis,according to the clinician's preference. As is known to those skilled inthe art, the prone, supine and decubitus position have their ownclinical merits in the different clinical applications.

Hybrid Tracking Methodology

The following describes another tracking methodology according to thepresent invention that uses a combination of passive tacking and encodertracking, and thus forms a hybrid tracking methodology. In this hybridmethodology, an initial position of the interventional device in scannercoordinates is obtained by segmenting fiducial markers 871 a-d (FIG. 26)placed on the interventional device on MR images. In an illustratedembodiment, there are two passive fiducial marker tubes 871 a,bincorporated into the main axis of the interventional device and twofiducial marker tubes 871 c,d placed parallel to the needle channel.Segmenting these four markers on the images obtained using an MRIprocess allows one to calculate the position of the main axis and theneedle axis, thus defining the initial position of the device. Suchsegmentation is done manually or automatically by control software.

In illustrative embodiments and with reference to FIGS. 30-31, insteadof acquiring axial image sets along the axes, which would take severalminutes, after localizing the end effector within the natural orartificial opening in the body, MR scout images are acquired and 3 ofthe four fiducial markers 871 a-d are found on the scout images so as todefine a sagittal plane as illustrated in FIG. 30. Thereafter a slab ofisotropic sagittal images (e.g., a thin slab—1 mm×1 mm×1 mm) areacquired in the plane of the markers. This reduces the imaged volumesignificantly and therefore reduces scan time.

In order to achieve easy segmentation of the markers, the sagittalimages are reformatted using the scanner software as axial images alongthe main axis of the device and along the needle axis of the device. Asshown in FIG. 31, the images are reformatted as axial images along thedevice and needle axis respectively to obtain circular cross-sections ofthe markers.

When the fiducial markers are tubular, the tubular markers appear ascircles on the reformatted axial images as illustrated in FIG. 28, thusallowing fast and easy segmentation and definition of the center pointsas locations on the main axis and parallel to the needle axisrespectively. The position of the two axes can then be calculated,defining the 6-DOF position of the device. Reference also should be madeto the discussion regarding Example two concerning the tracking accuracyevaluation.

Motion of the interventional device along its degrees of freedom isencoded with use of the position encoders 842, 844, which as indicatedherein can be any of a number of devices or encoders known to thoseskilled in the art including electrical, optical, opto-electrical ormechanical encoders. The three degrees of freedom to reach a target arerotation of the device, change of the needle angle and insertion of theneedle. Each of these degrees of freedom is encoded separately by therespective positioning encoder 822,844. In the illustrated embodiment,two rotational positioning encoders 822,824 are used to encode rotationand change in needle angle while the needle insertion depth is readmanually using the scale on the needle. It is within the scope of thepresent invention for the interventional device to further include atranslational positioning encoder to provide a signal of thetranslational movement of the needle as it is being inserted. It also iswithin the scope of the present invention to include manual ormechanical encoders for the rotation and needle angle so as to therebyprovide a redundant encoding system.

Signal Intensity Correction with Tracking

As is known to those skilled in the art, the intensity of the signaldetectable by an MRI antenna or coil varies as a function of thedistance from the coil or antenna because of signal losses. Thus, thecontrast between light and dark regions can be misleading because of thevariation in the intensity of the signal being detected. As is known tothose skilled in the art, the spatial distribution of the signalstrength detected by the coil can be calculated or experimentallydetermined in advance of its use and thus algorithms can be developedfor a given coil or antenna to correct for this variation in signal.These algorithms, however, are based on the assumption that the coil orantenna and/or the subject being imaged will not move or be moved duringthe acquisition of image data. If such movement occurs then there is noway to correct for signal intensity variations in the new spatialarrangement or location.

As the present invention continuously monitors and knows the location ofthe imaging coil, the present invention also features a methodology forcorrecting signal intensity using tracking. In the present invention,the location of the interventional device is tracked during theinterventional procedure and so the position of the imaging coil 164,placed on the sheath 852 also is easily determined. In other words, ifthe imaging coil 164 is moved with respect to the tissue, the trackingmethodology of the present invention provides a mechanism by which thenew spatial location of the imaging coil in the Cartesian coordinates ofthe scanner can be determined. Thus, using the known field distributionof the imaging coil and the determined spatial location of the imagingcoil, an image intensity correction scheme is run for all acquiredimages, resulting in a homogenous signal intensity distribution (e.g., acorrection is made to the as-is signal intensity to produce a uniformimage). Thus, by using the tracking information, the signal intensitycorrecting methodology of the present invention can correct signalintensity on the fly even when the imaging coil is moved to a newlocation.

The use of the interventional devices 100, 500, 800, 900 of the presentinvention as well as related systems, apparatuses and methods can bebest understood from the following discussion along with FIGS. 15-17.Reference shall be made to the foregoing discussion regarding FIGS. 1-14and 26-30 for other details and features not otherwise describedhereinafter. For purposes of discussion, the following describes the useof such an interventional device in connection with biopsy and treatmentprocedures for the prostate including accessing the prostate via therectum. This shall not be construed as limiting the device and relatedsystems, methods and apparatuses to this particular application. It iscontemplated that the interventional devices 100, 500, 800, 900 of thepresent invention as well as related systems, apparatuses and methodscan be adapted for use in connection with a wide range of diagnosticand/or treatment procedures for accessing the male prostate andsurrounding tissues via the rectum, accessing tissues of the female bodythrough the vagina and cervix and accessing body tissues via alaparoscopic portal. Such accommodation for such different applicationscan be achieved for example, by appropriate re-configuring and sizingthe end-effector 150, 525, 850, 950 to fit the requirements of a givenapplication.

A system 1000 according to the present invention is shown in FIG. 15.Prior to the surgical, diagnostic or treatment procedure, and while thepatient is still outside the gantry, the interventional device 100, 500,800, 900 is secured to the table, bed or platform of the scanner orimaging apparatus with an adjustable mounting mechanism such as theexemplary positioning apparatuses 400, 600, 1200 described herein. Theadjustable mounting mechanism or positioning mechanisms 400, 600, 1200allow flexible positioning of the interventional device 100, 500, 800,900 with respect to the subject or patient as herein described.

In order to achieve an initial position, the adjustable mountingmechanism is unlocked. The subject or patient is positioned comfortablyon the platform, bed, table or couch of the scanner or imaging apparatusin a prone, supine or decubitus body position (supine body position withthe pelvis slightly elevated is illustrated). The interventional device100, 500, 800, 900 is adjusted so its end piece, the end-effector 150,525, 850, 950 is aligned with the rectum. The end-effector 150, 525,850, 950 of the device is inserted into the rectum, in same way astransrectal ultrasound probes are used for brachytherapy implants. Theend-effector sheath 152, 525, 850, 950 makes contact with the rectum,thus leaving the needle carrier 154 or inner member movable inside thesheath. The sheath prevents movement of the needle carrier 154 or theinner member 854 from causing mechanical distortion to the rectum walland prostate. After a satisfactory initial position is achieved, theadjustable mount is secured to hold this position. Using the slidingtable of the scanner, the patient and interventional device are movedinto the bore of the scanner's magnet.

The MRI scanner produces signals with the subject or patient and devicein the field, at the same time. Using signal processing tools, thespatial relationship between the interventional 100, 500, 800, 900device and the coordinate system of the MRI scanner is determined asdescribed herein. The MRI images are transferred onto a computer 1010that produces three-dimensional graphical representation of theinterventional device superimposed on anatomic images. The physician ormedical personnel interacts with the display and selects the targetpoint for the needle 350 (e.g., target point for the tip of the needle).The computer 1010 calculates the coordinate transformation to guide theend effector and the needle 350 from its current position to theselected target position. In other words, the computer 1010 determinehow much to rotate and/or translate the end effector from its presentposition to a final position where the needle exit port 175 is at alocation for deployment of the needle 350 and how much to insert theneedle so the needle (e.g., the tip of the needle) will arrive at thethree-dimensional coordinates corresponding to the target location.

It should be recognized that the interventional device of the presentinvention allows a surgeon or medical personnel to image the endeffector using any one or a combination of active tracking mechanisms,passive fiducials and/or the positioning encoders as described hereinduring such rotation and translation to dynamically adjust for anychanging conditions as well as to verify that the needle carrier hasrotated and/or translated the desired amount before the needle isdeployed or inserted into the tissues of the subject. In addition, thesurgeon or medical personnel can image the tissue volume including thetarget tissue site to verify that the needle has been deployed to theintended target location. Consequently, the devices, systems and methodsof the present invention, allow a surgeon or medical personnel todetermine the parameters to control movement of the end-effector 150,525, 850, 950 and needle 350 so as to reach a target site within asubject and to verify placement or deployment of the needle to thedesired target site before a biopsy is taken or treatment is undertaken.

It should be recognized that the foregoing could not be readilyaccomplished using conventional procedures, techniques and devices. Suchconventional techniques, devices and systems typically involve manualmanipulation of an end-shooting type of device so that the end of thedevice is pointed at the volume of tissue including the target site.Because the needle and imaging device (e.g., ultrasound crystal) are atthe end of the device, the surgeon or medical personnel have to pushagainst the subject's rectum and/or anus in such a way so the body ofthe device is positioned within the rectum so the end is pointed in thedesired direction. In other words, for conventional devices, systems andtechniques, the body of the device being inserted into the rectum cannotbe aligned with the rectum for insertion. In addition to creating thepotential pain to the subject at least following the procedure, theprocess increases the risk of damage, trauma or insult to rectaltissues. In addition, because there is no practical way usingconventional devices, methods and systems, to pre-determine and maintaindirection or the position of the device end with respect to the targetsite, the user cannot determine precisely how much to move the devicefrom a given location to a final position before a needle is inserted.

It is contemplated that the interventional device 100, 500, 800, 900,methods and systems of the present invention are to work with or embodycomputational image guidance techniques as described herein. Forexample, fiducial markers with known geometric distribution areincorporated with the end-effector 150, 525, 850, 950 preferably in apre-established arrangement. Images are acquired with the interventionaldevice and patient/subject together in the field of view of the scanneror imaging apparatus. The digital images are transferred from thescanner to the planning computer 1010 via local area network or othersuitable connection. As described herein, using any one or a combinationof active tracking coils, passive fiducials and/or position encoders,the planning computer 1010 calculates the location and orientation ofthe end-effector 150, 525, 850, 950 with respect to the imager. Theoperator/user selects the target within the prostate for example on thecomputer screen and the computer 1010 calculates the location of thetarget with respect to the imager. Using a priori geometric informationof the end-effector 150, 525, 850, 950 the computer 1010 determines thespatial relationship between the current and the intended positions ofthe device.

The computer 1010 calculates three parameters for controlled motion:translation length for the end-effector 150, 525, 850, 950 rotationangle for the end-effector, and insertion length for the needle 350. Theprogram displays this information to the user, who can actuate theinterventional device 100, 500, 800, 900 accordingly. The three stagesof motion are kinematically decoupled in the interventional device andthus can be executed sequentially. This enables the user to acquire newimage upon completing a phase of the motion and determine whether thesequence of motions was calculated and executed correctly. The abovedescribed image guidance mechanism is equally applicable with MRI, CT,X-ray, and ultrasound imaging.

There are described above two different techniques or methodologies forpositional tracking of the end effector and/or needle; one techniqueinvolves a hybrid tracking technique involving the use of passivefiducials and position encoders and the other technique involves the useof a number of tracking coils. In the first technique, theinterventional device embodies a number of passive fiducials in a presetgeometric arrangement and includes position encoders to provide positioninformation regarding rotational and translational movement of the endeffector after initially establishing a position of the interventionaldevice within the natural or artificial body opening.

As described herein, the initial position of the end effector and thusthe components thereof, is first determined using MRI imaging data andthe passive fiducials. Thereafter, the position encoders provideposition data of the rotational and/or translational movement of the endeffector within the body opening after establishing the initialposition. As also described herein, using the scale on the medicaldevice or another position encoder, the position of the inserted needleor medical device can be determined. Thus, the computer 1010 can computethe kinematic sequence for the individual motion stages: the length oftranslation of the end-effector inside the rectum, the degree ofrotation of the end-effector inside the rectum, and the depth ofinsertion for the needle 350. The order of translation and rotation areinterchangeable, but both are completed before the needle 350 isinserted into the tissues. Alternatively, these can be computedmanually.

As to the other technique involving use of tracking coils, three imagingcoils 170 a-c are situated in the end-effector 150 of the interventionaldevice 100. Each imaging coil winds around a small capsule containinggadolinium solvent, in order to provide a strong signal in the vicinityof the coil. Two coils 170 a-b are located in the central axis of theend-effector 150, to encode translational motion of the interventionaldevice, more particularly translational motion of the needle carrier154. The third imaging coil 170 c is located off central axis, in orderto encode rotation around the central axis. As also indicated herein,the interventional device of the present invention can be configured soas to include one or more devices or sensors as is known to thoseskilled in the art that can determine translational and/or rotationalmotion of the carrier member without the use of an external imagingapparatus. Such a position determining sub-system can be used alone orin combination with the external imaging apparatus to ascertain anamount of rotational and/or translational motion of the carrier member.

Thus and in regard to this particular aspect of the invention, thecomputer 1010 computes the kinematic sequence for the individual motionstages, the length of translation of the end-effector inside the rectum,the degree of rotation of the end-effector inside the rectum, and thedepth of insertion for the needle 350. The order of translation androtation are interchangeable, but both are completed before the needle350 is inserted into the tissues.

Referring now also to FIG. 16 there is shown a schematic view of theend-effector and the method of targeting with the a 3-DOF interventionaldevice. The computer 1010 can also simulate the sequence by moving thegraphical model of the interventional device being displayed, so thatthe physician or medical personnel can verify that the calculatedsequence of motion would take the needle 350 from its current positionto the pre-selected target position. As indicated above, the computer1010 also displays the three motion parameters to the operator.

There also is illustrated in FIG. 17 positioning of an end-effectorwithin the rectum of a canine as well the deployment of the needle fromthe needle carrier into the tissues. This generally illustrates that thefirst imaging technique can visualize the needle 350 and theend-effector 150 after the needle is deployed and the position of theneedle with respect to tissues and/or organs of the subject.

In further embodiments, the first technique also includes a calibrationmethodology to determine the signal center of each MRI registration coilwith respect to the needle in the end-effector. This information isconstant for the entire lifetime of the device, provided the same imageacquisition and processing parameters are used during operation. Asillustrated in FIG. 18, two tubes filled with gadolinium solventproducing a strong image signal are applied to the end-effector. Inparticular, a first tube is placed inside the end-effector in itscentral axis, while the second tube is attached to the needle 350 in away that the central axes of the tube and the needle coincide. Theend-effector/interventional device is carefully imaged in a MRI scannerand the central axes of the two tubes as well as the positions offiducial coils are reconstructed from the high-resolution volumetricdata. Using this information one determines the three dimensionalrelationship between the trajectory of the needle and the threeregistration coils of the end-effector.

According to another embodiment, the methodology of the presentinvention includes using visual guidance to navigate an interventionaldevice 100, 500, 800, 900 of the present invention. In this embodiment,the user or medical personnel observes real-time or near real-time imagedata from the scanner or imaging apparatus, visually identifies theneedle in the image and its location with respect to a target site. Theuser, physician, medical personnel using hand-eye coordination,continually actuates and repositions the interventional device till theend-effector and needle reaches the intended position or target site. Inthis way, the user, physician, or medical personnel manually navigatesthe interventional device so the needle 350 is deployed to the targetsite. Consequently, a plurality or more of placements or deployments ofthe needle 350 may be required before satisfactory needle placement isachieved.

As described above, there are two different techniques or methodologiesfor positional tracking of the end effector and/or needle; one techniqueinvolves a hybrid tracking technique involving the use of passivefiducials and position encoders and the other technique involves the useof a number of tracking coils. In the case where the interventionaldevice embodies the hybrid tracking methodology, the initial positiondata and the movement position data are sent to the treatment monitoringcomputer 1010. The computer 1010 processes the transmitted position dataand the three parameters of motion (translation, rotation, insertiondepth) are calculated/recalculated, enabling real-time dynamic controlof the interventional device such as for example, by adjusting theactuation of motors or other manual or automatic actuation devices ofthe interventional device. It also is contemplated, and thus within thescope of the present invention, that when a surgeon points and clicks ona target in a computer screen, a robot controls the operation of theinsertion stage so as to move the needle 350 and insert it into thetarget.

In the case where the interventional device embodies tracking coils,while the actuation of the interventional device is in progress, the MRIscanner 1020 collects position data and sends the position dataimmediately to the treatment monitoring computer 1010. The computer 1010processes the image data and visualizes the current image, with themodel of the interventional device superimposed in the scene, allowingthe physician to monitor the motion of the interventional device and/orneedle 350 thereof toward its target. The three parameters of motion(translation, rotation, insertion depth) are recalculated in eachimaging cycle, enabling real-time dynamic control of the interventionaldevice such as for example, by adjusting the actuation of motors orother actuation devices of the interventional device. It also iscontemplated, and thus within the scope of the present invention, thatwhen a surgeon points and clicks on a target in a computer screen, arobot controls the operation of the insertion stage 250 so as to movethe needle 350 and inserts it into the target, under real-time imagingsurveillance but without manual intervention.

In addition, to use of the interventional device 100, 500, 800, 900 ofthe present invention to take tissue biopsies, it also is contemplatedthat the scope of the methodologies and systems of the present inventionincludes delivery of therapeutic mediums, medical devices via theinserted needle and that such insertion can be performed one or moretimes and at different locations or target sites within a predeterminedvolume of tissues of the subject. In particular embodiments, it iscontemplated that the placement of the needle 350 within the prostate orother tissues of the body (e.g., cervix or vagina) provides a mechanismby which a therapeutic medium (including but not limited to drugs,genes, viruses and photodynamic substances) or diagnostic agents(including but not limited to molecular imaging agents) can be deliveredto a desired target site(s) using the inserted needle of theinterventional device. It also is contemplated that the cannula or lumenformed by the inserted needle can be utilized to insert medical devicesthrough the needle and so as to be localized to the target site(s) so asto perform one of brachytherapy, or tissue ablation (including thermal,cyro, ultrasonic, chemical ablation). Further, it also is contemplatedthat the interventional device and related systems and methods can beadapted for use with any of a number of medical imaging or scanningtechniques including conventional X-ray, fluoroscopy, bi-planarfluoroscopy, CT X-ray, MRI, and ultrasonic imaging as well as any othertechniques referred to herein.

As indicated above, the interventional devices and related systems, andapparatuses of the present invention are configured and arranged so asto administer/deliver a therapeutic medium to the target tissues of atarget site. The therapeutic medium can comprise a therapeutic agent ora therapeutic agent in combination with a contrast agent to facilitatethe imaging (e.g., MR imaging) of the therapeutic agent. In the presentinvention, therapeutic agent shall be understood to encompass orinclude, but are not limited to drugs, genes, nucleic acid moleculesincluding encoding different types of nucleic acid molecules, anangiogenic factor, a growth factor, a chemotherapeutic agent, aradionuclide, a protein, a polypeptide, a peptide, a viral protein, alipid, an amphiphile, a nuclease inhibitor, a polymer, a toxin, a cell,and modified forms and combinations thereof that are used in therapeuticprocedures in connection with the injury, insult, trauma or ischemia tothe tissues or cells of the target site that is accessed via a lumen orbody cavity of the mammalian body, more particularly a human body, morespecifically, the vascular system of a human body. In addition, thetherapeutic agent can be in an encapsulated form for long term sustaineddelivery to the target tissues.

The nucleic acid molecule is preferably provided in a nucleic aciddelivery vehicle which is lipid-based, viral-based, or cell-based. Morepreferably, the vector comprises a gene operably linked to an expressioncontrol sequence. In one aspect, the nucleic acid molecule comprises asequence encoding a polypeptide for preventing, correcting and/ornormalizing an abnormal physiological response, such as a disease.Exemplary polypeptides include, but are not limited to, hirudin, tissueplasminogen activator, an anchored urokinase activator, a tissueinhibitor of metalloproteinase, proliferating cell nuclear antigen, anangiogenic factor, a tumor suppressor, a suicide gene and aneurotransmitter. The vector may comprise sequences to facilitate itsdelivery to, or expression in, a target cell. For example, the vectormay comprise a marker gene (e.g., encoding a fluorescent protein) and/oran origin of replication for a host cell and/or target cell.

In the case where the therapeutic medium is being delivered and theparticular imaging technique is being performed to track and observe theefficacy of such delivery, the therapeutic medium is a therapeuticcomposition that includes a therapeutic agent as hereinabove describedand a contrast agent appropriate for the particular imaging techniquebeing utilized. In a particular embodiment, the imaging technique is anyof a number of MR/NMR imaging techniques and thus the contrast agent isa magnetic resonance imaging contrast agent.

MRI contrast agents primarily act by affecting T1 or T2 relaxation ofwater protons. Most MRI contrast agents generally shorten T1 and/or T2.When contrast agents shorten T1, this increases signal intensity on T1weighted images. When contrast agents shorten T2, this decreases signalintensity particularly on T2 weighted pulse sequences. Thus, preferably,contrast agents used in the invention have adequate nuclear orrelaxation properties for imaging that are different from thecorresponding properties of the cells/tissue being imaged. Suitablecontrast agents include an imagable nucleus (such as ¹⁹F),radionuclides, diamagnetic, paramagnetic, ferromagnetic,superparamagnetic substances, and the like. In a preferred aspect,iron-based or gadolinium-based contrast agents are used, whereIron-based agents include iron oxides, ferric iron, ferric ammoniumcitrate and the like. Gadolinium based contrast agents includediethylenetriaminepentaacetic (gadolinium-DTPA). Manganese paramagneticsubstances also can be used. Typical commercial MRI contrast agentsinclude Omniscan, Magnevist (Nycomed Salutar, Inc.), and ProHance.

In one preferred embodiment, gadolinium is used as the MRI contrastagent. Less than about 28.14 mg/mL gadolinium (such as less than 6%Magnevist) is an adequate concentration for imaging and is minimallydestructive of nucleic acid delivery vehicles. However, it is wellwithin the skill of those in the art to vary and optimize the amount ofcontrast agent to add to the compositions depending on the nature of thecontrast agent (e.g., their osmotic effects) and the length of timeduring which a target cell is exposed.

In other embodiments, the composition comprises a pharmaceuticallyacceptable carrier. Preferably, the carrier is non-toxic, isotonic,hypotonic or weakly hypertonic and has a relatively low ionic strength(e.g., such as a sucrose solution). Furthermore, it may contain anyrelevant solvents, aqueous or partly aqueous liquid carriers comprisingsterile, pyrogen-free water, dispersion media, coatings, andequivalents, or diluents (e.g. Tris-HCl, acetate, phosphate),emulsifiers, solubilizers and/or adjuvants. The pH of the pharmaceuticalpreparation is suitably adjusted and buffered in order to be appropriatefor use in humans or animals. Representative examples of carriers ordiluents for an injectable-composition include water or isotonic salinesolutions which are preferably buffered at a physiological pH (e.g.,such as phosphate buffered saline, Tris buffered saline, mannitol,dextrose, glycerol containing or not polypeptides or proteins such ashuman serum albumin). The compositions also can comprise one or moreaccessory molecules for facilitating the introduction of a nucleic aciddelivery vector into a cell and/or for enhancing a particulartherapeutic effect.

The foregoing is illustrative and shall not be considered limiting as tothe drugs or therapeutic compounds or agents, carriers, and accessorymolecules that can be used to comprise the therapeutic medium of thepresent invention. Applicants also herein incorporate by reference theteachings and disclosures in their entirety of pending U.S. Ser. No.10/116,708 entitled Imaging Nucleic Acid Delivery and in particularthose teachings and disclosures of the various therapeutic agentsdescribed therein, which invention is assigned to the assignee of thepresent invention.

Example 1

A mechanically actuated, transrectal needle guide is used to perform MRguided needle placements in the prostate. With a microcoil trackingmethod, the position and orientation of the biopsy needle guide in theMR imaging volume (60 msec) could be quickly and accurately located.Knowing the position of the biopsy needle allows for acquisition ofrealtime images of a plane including the needle and registration of theneedle position with previously acquired, high-resolution images of theprostate. In four canine studies, the functionality and applications ofa system was demonstrated.

A thin-walled, cylindrical plastic sheath (Delrin plastic, DuPont Inc.,Wilmington, Del.) with a radius of 1.5 cm is inserted into the subject'srectum, forming a stable and stationary entry point through which theprostate can be accessed. Integral to the sheath is a single turnimaging loop (with a diameter of 2.5 cm) for local imaging of theprostate. The sheath has a window, located within the imaging loop, suchthat a needle can be advanced from inside the sheath, through the rectalwall, and into the body of the prostate.

Next, a cylindrical needle guide, also made of Delrin plastic, is placedwithin the rectal sheath. As the needle guide is coaxial with the rectalsheath, the needle guide is free to rotate and translate within thecavity formed by the sheath without causing deformation of thesurrounding soft tissue. Integral to the needle guide are (1) threemicrocoil fiducials and (2) a curved channel for the needle. Note thatbecause the needle channel is curved, the needle can be inserted alongthe axis of the needle guide and emerge out of its lateral wall,allowing for access to the prostate through the window in the stationaryrectal sheath.

Next, both the rectal sheath and the needle guide are affixed to apositioning stage made of Nylon plastic (QTC, New Hyde Park, N.Y.) andDelrin. First, the positioning stage serves to hold the rectal sheathstationary within the subject's rectum. A linear track (aluminum rail,80/20 Inc., Columbia City, Ind.) and a polyamide plastic articulated-armwith six joints that are operably connected to the positioning stageallow for full mobility of the positioning stage, such that it can beeasily docked with the rectal sheath, at which point the linear trackand articulated arm are locked down to prevent any subsequent motion.

In addition to holding the rectal sheath stationary, the positioningstage contains a screw drive mechanism that allows for both rotation andtranslation of the needle guide. This device converts rotation of twoconcentric control rods (Epoxy tubing, TAP Plastics, Dublin, Calif.),both of which extend outside of the scanner bore, into rotation andtranslation of the needle guide. This allowed the operator to positionthe needle guide while the subject is within the closed bore scanner.

As the entire device is constructed with a coaxial design, the centralaxis offers an unobstructed path for insertion of the needle. The depthof needle insertion is controlled using a variable offset stop that isinserted at the back of the device before introducing the needle. An 18G coaxial biopsy needle (MRI Devices Daum GmbH, Schwerin, Germany) isinserted such that the needle tip emerges from the side of the needleguide.

Device Tracking, Prostate Targeting, and Realtime Imaging

MR pulse sequences and hardware were designed to facilitate targetedneedle placement in the prostate within a GE 1.5 T CV/i MRI scanner with4 independent receiver channels. Three microcoil fiducials wereintegrated within a transrectal needle guide, each connected to aseparate receiver channel. To determine the position and orientation ofthese coils, twelve 1-D dodecahedrally spaced readouts were collected(TE 2.3 msec, TR 5.0 msec, BW+/−64 KHz, FA 1°, FOV 40 cm, 256 readoutpoints), allowing for coil localization [Dumoulin C L, Souza S P, DarrowR D. Real-time position monitoring of invasive devices using magneticresonance. Magn Reson Med 1993; 29:411-415; Derbyshire J A, Wright G A,Henkelman R M, Hinks R S. Dynamic scan-plane tracking using MR positionmonitoring. J Magn Reson Imaging 1998; 8:924-932]. The coil localizationscan occupied ˜60 msec. Microcoil location errors due to gradientnonlinearity were removed using gradient dewarping algorithms (GEMedical Systems, Waukesha, Wis.).

Given the position of the three microcoil fiducials in the MR coordinatesystem and the location of a given intraprostatic target (also in the MRcoordinate system), the remaining problem is to determine (1) therotation and translation necessary to position the needle guide suchthat the needle trajectory is aligned with the target and (2) the amountof needle insertion necessary to reach the target. This can becalculated using a set of coordinate transformations—assuming that therelationship between the microcoil positions, the device axis, and theneedle trajectory are all known. These relationships are establishedusing a device calibration scan in which Gd-DTPA (Magnevist, BerlexLaboratories, Wayne, N.J.) fiducial tubes define the device axis and theneedle trajectory (the same, single calibration scan was used for allstudies described here). In addition to determining the rotation andtranslation necessary to reach the target site, the calibration of themicrocoil positions with the needle trajectory allowed for definition ofa scan plane that includes both the needle path and the device axis.‘Realtime’ images were acquired based on the current position of themicrocoil fiducials, such that the needle could be visualized as it wasinserted into the prostate.

All experiments were performed on a GE 1.5 T CV/I MRI scanner (GEMedical Systems, Waukesha, Wis.). A fast gradient-echo pulse sequence(FGRE) was modified to allow for alternating acquisition of themicrocoil-tracking readouts (i.e. the twelve, dodecahedrally spacedreadouts) and realtime FGRE images. After the location of each coil wasdetermined, the position and orientation of the imaging plane is definedsuch that the realtime FGRE image slice tracked with the position of theneedle.

Realtime data processing and display were performed using a Sun Ultra IIWorkstation (Sun Microsystems, Mountain View, Calif.) connected to thescanner with a high-bandwidth data bus (Bit3 Corporation, St Paul,Minn.). In the current implementation, the tracking sequence takes 60msec; image processing, communication, and scan plane localizationoccupies 150 msec; and imaging takes 300 to 1300 msec—yielding framerates of 0.7 to 2 fps (depending predominantly on image acquisitiontime). Images were acquired using a rectal imaging coil while the otherthree receiver channels were used for the microcoil fiducials.

Animal Protocol

All animal protocols were reviewed and approved by the Animal Care andUse Committee at the Johns Hopkins University School of Medicine. Fourmongrel dogs weighing approximately 25 kg were anesthetized with a bolusinjection of thiopental and maintained on 1% isoflurane throughout theexperiment. An intravenous catheter was placed in the right jugular veinfor fluid administration and a Foley catheter was inserted to aid instabilizing the prostate and to define the position of the prostaticurethra. The animals were placed prone on the scanner table with thepelvis slightly elevated 10 cm) with a 5-inch surface coil on theanterior surface of the abdomen at the level of the prostate. The rectalsheath was inserted into the rectum and docked with the positioningapparatus, which was then locked in place.

Needle Placement Protocol

In the first animal study, the accuracy of needle placement was testedin-vivo. After the animal was positioned in the scanner, T1 weighted FSEimages of the prostate and surrounding anatomy were acquired (TE 9.2msec, TR 700 msec, BW+/−31.25 KHz, ETL 4, FOV 16 cm, slice thickness 3mm, 256×256, NEX=4, scan time 3:00). Two receiver channels were used forthese images: one for the 5-inch surface coil and one for the rectalcoil. In these images, a target was selected within the body of theprostate and entered into the realtime control program. Scanning wasthen switched to the realtime FGRE imaging and tracking sequence.

While running the realtime FGRE imaging and tracking sequence, theoperator is able to rotate and translate the needle guide from the mouthof the scanner bore using the control rods. On a scan room flat paneldisplay, the operator watches both the realtime image slice, showing thetrajectory of the needle, as well numerical values indicating thecurrent amount of rotation and translation necessary to set the correctneedle trajectory. As the needle guide is moved closer to the targetposition, these numbers move to zero—indicating that no more rotation ortranslation is necessary.

Once the needle guide on the proper trajectory, the insertion stop isset to the proper depth (also indicated on the flat panel display) andthe needle is pushed until it is flush with the stop. The insertion ofthe needle can be visualized on the scan room display and once in place,the needle tip will be at the desired target location.

To confirm the location of the needle tip, a second set of T1 weightedFSE images were acquired. This protocol was repeated for four separateneedle insertions.

Intraprostatic Injection Protocol

To demonstrate MR monitored injection therapies, intraprostaticinjections were preformed in two canine subjects. Similar to the needleplacement protocol, targets in the prostate were selected on axial T1weighted FSE images and the needle tip was placed at these locationsusing the realtime FGRE imaging and tracking sequence. After the coaxialneedle was placed, the trocar (i.e. an inner stylus) was withdrawn,leaving only the 18 G cannula (i.e., a hollow metal tube) in place. Thisprovided a conduit through which injections into the body of theprostate could be performed.

In this demonstration, a mixture of 0.4% Trypan Blue (Sigma-Aldrich, St.Louis, Mo.) and 30 mM Gd-DTPA (Magnevist, Berlex Laboratories, Wayne,N.J.) was injected, in particular 0.3 mL of this solution was injectedinto the prostate. During the injection, the flow of the mixture wasmonitored using a high flip-angle, RF-spoiled, gradient echo imagingsequence (FSPGR, TE 1.5 msec, TR 6 msec, FA 90°, BW+/−62.5 KHz, FOV 16cm, slice thickness 10 mm, 256×160, 0.96 sec/image). The location of theinjected solution was determined by comparing gradient echo axial imagesacquired both before and after the injection (FSPGR, TE 2.0 msec, TR 80msec, FA 60°, BW+/−31.25 KHz, FOV 16 cm, slice thickness 3 mm, 256×256,NEX 4, scan time 1:20).

Brachytherapy Seed Placement Protocol

In a fourth canine, the use of the device for MR guided brachytherapyseed placement was demonstrated. Targets were selected and the trocarand canula were placed, as described previously. Then, to insert thetitanium brachytherapy seeds (OncoSeed blanks, Medi-Physics Inc.,Arlington Heights, Ill.), the trocar was withdrawn, leaving the hollowcannula in place within the prostate. A brachytherapy seed was insertedinto the cannula and then advanced to the end, but not out, of thecannula by pushing it with another trocar. With the seed at the end ofthe cannula, the cannula was withdrawn slightly while holding the trocarstationary, causing the brachytherapy seed to be ejected into theprostate tissue. Subsequently, the trocar and cannula were bothwithdrawn together.

Three seeds were placed using this technique. The location of the needleand of the seeds was confirmed using T1 weighted FSE images (TE 9.2msec, TR 700 msec, BW+/−31.25 KHz, ETL 4, FOV 16 cm, slice thickness 3mm, 256×256, NEX=4, scan time 3:00).

Results

In the first canine subject, accurate needle placement within the bodyof the prostate is demonstrated. The results of this study aresummarized in FIG. 19. In sequential order, four targets were selectedfrom T1 weighted FSE images (FIG. 19, top row). Having placed the needleusing the FGRE real time imaging and tracking sequence, FSE images wererepeated to confirm placement of the needle by visualizing the needlevoid (FIG. 19, bottom row). In all cases, the end of the needle artifactwas found in the same image slice as the target. Moreover, the center ofthe needle tip void was found within 2 mm of the selected target. Notealso that there is minimal motion of the prostate upon insertion of theneedle.

For interpretation of these results, it is useful to examine theartifact created by the 18 G MR compatible needle. FIG. 20 shows theartifact created both by the needle and by a brachytherapy seed.Artifacts were aligned by placing the physical objects at the interfaceof gadolinium doped and gadolinium free gel blocks. Note that the tipvoid is a circular bloom that is centered on the physical end of theneedle, as has been previously reported when the needle is alignedapproximately parallel to B₀ with the tip toward the positive magnetpole [Liu H, Martin A J, Truwit C L. Interventional MRI at high-field(1.5 T): needle artifacts. J Magn Reson Imaging 1998; 8:214-219]. In allcases, because of the design of the needle placement system, the needleis approximately parallel to B₀ and therefore, the artifact provides agood estimate of the needle tip position.

In two canine subjects, the use of the system for MR monitoredintraprostatic injections was demonstrated. First, a target within thebody of the prostate gland was selected and the needle was positioned asdescribed in the previous section. Then, the trocar was withdrawn,leaving the cannula as a conduit into the prostate. A mixture of 30 mMGd-DTPA and 0.4% Trypan Blue [Yang X, Atalar E, Li D, et al. Magneticresonance imaging permits in vivo monitoring of catheter-based vasculargene delivery. Circulation 2001; 104:1588-1590] was then injected intothe prostate. A high flip-angle, RF-spoiled, gradient echo acquisitionwas run during the injection of 0.3 mL of this solution. The box on thesagittal scout (FIG. 21, left image) shows the location of the timeseries images. Note that all of the injected contrast/dye solution staysconfined within the prostate. Therefore, it was confirmed—during theinjection—that the full, desired dose was delivered to the prostatetissue.

In FIG. 22, the distribution of the mixture as shown in the MR images iscompared with that revealed on histology. There is good correlationbetween the tissue enhancement (seen in the second column, after theinjection, but not in the first column, before the injection) and thetissue stained with the Trypan Blue dye (FIG. 22, third column).

In the next canine, the injection protocol was repeated as before. Inthis case, however, the injected contrast/dye solution is seen to leakout of the prostate and into the surrounding connective tissue (FIG.23). Therefore, it is known—during the procedure—that the desired dosehas not been delivered to the prostate. In FIG. 24, the presence ofTrypan Blue in connective tissue at the superior margin of the prostateis confirmed histologically.

In the last canine subject, the application of the system for placingbrachytherapy seeds within the prostate is demonstrated. The results ofthis study—in which three seeds were placed in the prostate—aresummarized in FIG. 25. As described previously, three targets wereselected, in succession, within the body of the prostate (FIG. 25, rowa) and the needle was placed using the realtime FGRE imaging andtracking sequence (FIG. 25, row b). As compared with the needleplacement study (FIG. 19), the tip of the needle artifact is seen toextend beyond the target point. This is because the brachytherapy seedsare placed at the end of the cannula, not at the end of the trocar. Thetrocar extends 2 mm past the end of the cannula. Therefore, for properseed deposition, the trocar must extend 2 mm past the target point, asseen in FIG. 25, row b.

In FIG. 25, row c, the seeds are placed in the prostate and the coaxialneedle has been removed. To interpret these results, refer to FIG. 20,where the artifact pattern for the brachytherapy seeds is displayed. Themain signal void is found at the end of the 4 mm seed that lies nearestto the positive pole of B₀. This corresponds to the black void seen inFIG. 25, row c. The body of the brachytherapy seeds extend 4 mm in theinferior direction from this void (in the direction of the targetlocation). The seeds lie within 3 mm of the selected target location.Also, note that intraprostatic bleeding, resulting from seed placement,can be seen near seeds 2 and 3 (i.e. the dark banding radiating towardthe edge of the prostate).

Example 2

Experimental Setup

The accuracy of the passive tracking method for determining the initialdevice position according to the tracking method of the presentinvention was tested in a phantom experiment. As shown in FIG. 32, aplate was built with three integrated channels. A channel representingthe device axis, a channel for the needle axis at a 40 degree angle(angle α) to the device axis, and a channel perpendicular to the deviceaxis placed 50 mm (distance d) away from the intersection point of thedevice and needle axis. Passive gadolinium marker tubes (Beekley Corp.,Bristol, Conn.), 8 mm in diameter and 15 mm long were positioned alongeach axis. While two markers were placed in the device and perpendicularchannel, the needle channel contained four markers. This setup yieldedvarious combinations of markers with varying distances to define theneedle axis. Therefore the effect of the distance between markers on theaccuracy could be studied. The experiments were conducted on a 3TPhilips Intera MRI scanner (Philips Medical Systems, Best, NL).

Referring now also to FIG. 33, the marker plate assembly was imaged in16 different random orientations in the MRI scanner and the images werereformatted along each of the three channels. The scan time for theisotropic 1 mm×1 mm×1 mm proton density (PD) weighted TSE sagittal imagesequence was 2 minutes and 30 seconds. The reformatted image setsyielded axial images along each channel with a slice thickness of 1 mm.Circles were manually fitted to each marker image and the center of thecircle was recorded, if the quality of the image was satisfactory. Thisprocess yielded, depending on image quality, between 2 and 10 circlecenter values per marker. Low quality images were mostly due to airbubbles in the marker tubes. The three line equations for the axes werecalculated from the marker center locations, using a least squaresfitting algorithm based on the singular value decomposition. From theaxes equations, the distance d, angle a and distance between axes werecomputed.

Experimental Results

There is provided in FIG. 34, a tabulation of the accuracy results forthe 16 different orientations. On the left half of the table allrecorded marker center locations were used to calculate each axis, onthe right half of the table, only one center location for each markerwas used. The different columns indicate which of the needle markerswere combined to compute the needle axis. Highlighted are the standardand the maximum deviation for the angle α, and the distance d. Thestandard and maximum deviation values in the right half of the table areonly slightly higher than in the left half, indicating that only onelocation per marker yields satisfactory accuracies, which can beachieved with a faster segmentation. Using all four markers to definethe needle axis in contrast to using markers 1 and 4 only, hardlyimproves the accuracy results. Consequently, adding more markers withinan axis does not provide considerably better accuracies.

Referring now to FIG. 35, there is shown a graphical view of max and stddeviation of error versus length between needle markers. The graph plotsangular and distance errors, highlighted in FIG. 35 in the right half ofthe table, over the distance of the markers, selected to obtain theneedle axis. A theoretical model of the dependency of the markerdistance on the error was obtained. Assuming a statistical error c fromdetermining the device axis and adding the error for the needle axis,the model yields a Δe=1/x+c dependency for the error on the distance x.The experimental results shown in FIG. 35 seem to fit this model.

Comparison of Micro-Coil and Passive Fiducial Tracking Accuracy

The accuracy performance of the hybrid tracking method according to thepresent invention was compared to the active tracking method, byobtaining error histograms of 36 active tracking orientations and of 16passive tracking orientations. Since the hybrid tracking method iscomprised of initial passive tracking and subsequent encoder tracking,an error model for the encoders was added to the passive trackingresults. The optical encoders, contemplated for use for the tracking inthe present invention, have a resolution of 0.25 degrees. Therefore arandom, zero mean error with uniform distribution and an amplitude of0.25 degrees was added to the passive tracking results to simulate thecombined error of the hybrid tracking method. For the passive trackingerror, the marker combination 1 and 3 with one circle per marker forsegmentation was selected for comparison to the active tracking. Markers1 and 3 are located at a distance of 45 mm from each other. Thisdistance between markers can be implemented in our device design, makingthis combination a logical choice.

Referring now to FIGS. 36A,B, there are shown histograms of angularerrors for the active tracking (FIG. 36A) and the hybrid tracking methodof the present invention (FIG. 36B). The accuracy results for the hybridtracking method are very promising, considering that with a reasonabledistance between markers of 45 mm, the maximum angular deviation lies at0.6 degrees. This is below the +/−1 degree error for, the activetracking.

CONCLUSION

The experimental results demonstrated that the hybrid tracking method ofthe present invention can be used for accurate tracking ofinterventional robotic devices. Since only one location per marker isenough to accurately compute an axis, segmentation and consequent axisdefinition for initial position tracking can be achieved relativelyquickly.

In sum, the hybrid tracking method of the present invention has a numberof advantages effects. Tracking errors using the hybrid tracking methodcompare favorably to existing tracking methods. The passive trackingportion of method of the present invention uses only standard MRI pulsesequences in contrast to the custom sequences that need to be developedand implemented when using active tracking. Also, the passive trackingportion of method of the present invention does not occupy any scannerreceiver channels. In addition, no custom programming on the MRI scanneris necessary, allowing the method to be employed easily in variousscanners. Further, the method does not require any electronic or metalparts on the interventional device ensuring complete MRI-compatibilityand MR-safety.

While active tracking methods such as micro-coils and gradient sensingremain the penultimate in their ability to provide extremely fastreal-time absolute 6-DOF position measurement, the hybrid trackingmethod of the present invention offers an alternative, providingequivalent accuracy, real-time relative tracking, but with far greaterease of deployment on different scanners as compared to existing activetracking methods.

Although a preferred embodiment of the invention has been describedusing specific terms, such description is for illustrative purposesonly, and it is to be understood that changes and variations may be madewithout departing from the spirit or scope of the following claims.

What is claimed is:
 1. A method for tracking movement of a movableportion of an interventional device disposed within a natural orartificial body opening, wherein the interventional device includespassive fiducial markers configured in a preset configuration andvisible in an image technique being used, position encoders operablycoupled to the movable portion so as to provide outputs representativeof movement of the movable portion, a sheath, and a needle channelconfigured to receive a needle therein, the method comprising: acquiringimage data of the passive fiducial markers, wherein a first subset ofthe passive fiducial markers is disposed along a main axis of theinterventional device, and a second subset of the passive fiducialmarkers is disposed along the needle channel at a location outside ofthe sheath, the needle channel defining a needle axis that isnon-parallel to the main axis; calculating positions of the main axisand the needle axis, respectively, based on the acquired image data ofthe passive fiducial markers; determining an initial position of themovable portion with respect to a given coordinate system according tothe calculated positions of the main axis and the needle axis; acquiringposition data from the position encoders as the movable portion is movedfrom the determined initial position; determining a displaced positionof the moveable portion relative to the determined initial position; anddetermining a position of the movable portion in the given coordinatesystem using the determined initial position and the determineddisplaced position.
 2. The tracking method of claim 1, furthercomprising the steps of: deploying the needle from the interventionaldevice and acquiring data representative of the amount of deployment;and determining a position of the needle in the given coordinate systemusing the determined initial position, the determined displaced positionand the data acquired representative of the amount of deployment.
 3. Thetracking method of claim 1, wherein the calculating of the positions ofthe main axis and the needle axis comprises: defining a plane withrespect to the passive fiducial markers; acquiring a slab of images inthe defined plane; reformatting the acquired image data as axial imagesalong the main axis and the needle axis; and calculating the positionsof the main axis and the needle axis, respectively, using information inthe axial images.
 4. The tracking method of claim 3, wherein thecalculating of the positions of the main axis and the needle axisfurther comprises: identifying cross-sectional images of the passivefiducial markers within the axial images; and calculating the positionsof the main axis and the needle axis, respectively, with reference tothe identified cross-sectional images of the passive fiducial markers.5. The tracking method of claim 4, wherein the calculating of thepositions of the main axis and the needle axis further comprises:calculating center points of the identified cross-sectional images ofthe passive fiducial markers; and determining the main axis and theneedle axis are respectively positioned along one or more of thecalculated center points of the identified cross-sectional images of thepassive fiducial markers.
 6. The tracking method of claim 5, wherein thepassive fiducial markers are tubular, and the calculating of the centerpoints of the identified cross-sectional images of the passive fiducialmarkers comprises: determining center points of circular shapes formedby the identified cross-sectional images of the tubular passive fiducialmarkers.
 7. The tracking method of claim 1, wherein the imagingtechnique is a MRI technique.
 8. The tracking method of claim 1, whereinthe first subset of the passive fiducial markers includes two or morepassive fiducial markers, and the second subset of the passive fiducialmarkers includes two or more passive fiducial markers.
 9. The trackingmethod of claim 1, wherein the acquiring of position data from theposition encoders comprises: defining degrees of freedom of theinterventional device according to the calculated positions of the mainaxis and the needle axis; and encoding motion along the defined degreesof freedom using the plurality of position encoders.